MECIR Manual - Cochrane

MECIR Manual ............................................................................... 3Key points and introduction ........................................................................ 3Development and consultation ...................................................................... 3Implementation of the Standards .................................................................... 4Acknowledgements ............................................................................ 4Versions and changes to MECIR .................................................................... 5How to cite the MECIR Standards .................................................................. 10Standards for the CONDUCT of new Cochrane Intervention Reviews (C1-C75) ...................................... 10Key points and introduction ....................................................................... 10Developing the protocol of the review (C1-C23) .......................................................... 10Setting the research question to inform the scope of the review (C1-C4) .......................................... 11Setting eligibility criteria for including studies in the review (C5-C13) ............................................. 12Selecting outcomes to be addressed for studies included in the review (C14-C18) .................................... 15Planning the review methods at protocol stage (C19-C23) ................................................... 17Performing the review (C24-C75) ................................................................... 18Searching for studies (C24-C38) ................................................................... 19Selecting studies to include in the review (C39-C42) ....................................................... 23Collecting data from included studies (C43-C51) ......................................................... 25Assessing risk of bias in included studies (C52-C60) ...................................................... 27Synthesizing the results of included studies (C61-C73) ..................................................... 30Assessing the quality of evidence and summarizing the findings (C74-C75) ........................................ 33Reference ................................................................................. 34Citation ................................................................................... 34Standards for the REPORTING of PROTOCOLS of new Cochrane Intervention Reviews (PR1-PR44) ....................... 34Key points and introduction ....................................................................... 34Reporting the review plan (PR1-PR44) ............................................................... 35Title and Authors (PR1-PR2) ..................................................................... 35Background (PR3-PR4) ......................................................................... 35Objectives (PR5-PR8) .......................................................................... 36Criteria for considering studies for this review (PR9-PR16) ................................................... 38Search methods for identification of studies (PR17-PR21) ................................................... 41Data collection and analysis (PR22-PR40) ............................................................. 42Acknowledgements (PR41) ...................................................................... 48Contribution of authors (PR42) .................................................................... 48Declarations of interest (PR43) .................................................................... 49Sources of support (PR44) ....................................................................... 49Citation ................................................................................... 49Standards for the REPORTING of new Cochrane Intervention Reviews (R1-R109) ................................... 49Key points and introduction ....................................................................... 50Reporting review conduct (R1-R55) ................................................................. 50Title and Authors (R1-R2) ....................................................................... 50Abstract (R3-R18) ............................................................................ 51Background (R19-R25) ......................................................................... 55Methods (R26) .............................................................................. 57Criteria for considering studies for this review (R27-R32) .................................................... 58Search methods for identification of studies (R33-R38) ..................................................... 60Data collection and analysis (R39-R55) ............................................................... 62Results (R56-R109) ........................................................................... 66Description of studies (R56-R72) ................................................................... 66Risk of bias in included studies (R73-R75) ............................................................. 70Effects of interventions (R76-R99) .................................................................. 70Discussion (R100-R101) ........................................................................ 76Authors' conclusions (R102-R103) .................................................................. 77Acknowledgements (R104) ...................................................................... 78Contribution of authors (R105) .................................................................... 78Declarations of interest (R106) .................................................................... 78Differences between protocol and review (R107-R108) ..................................................... 79Sources of support (R109) ....................................................................... 80Reference ................................................................................. 80Citation ................................................................................... 80

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Standards for planning, conduct and reporting of UPDATES of Cochrane Intervention Reviews (U1-U11, UR1-UR7) .............. 80Key points and introduction ....................................................................... 80Deciding on and performing an update (U1-U11, UR1-UR7) .................................................. 81Planning the update (U1-U5) ..................................................................... 81Conduct standards specific to updates (U6-U11) ......................................................... 83Reporting standards specific to updates (UR1-UR7) ....................................................... 85Citation ................................................................................... 88Translations of the MECIR Standards ................................................................ 88Key points and introduction ....................................................................... 88Japanese translation ........................................................................... 89Russian translation ........................................................................... 89Spanish translation ............................................................................ 89

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MECIR Manual

Methodological Expectations of Cochrane Intervention Reviews(MECIR)Version February 2021

Standards for the conduct and reporting of new Cochrane Intervention Reviews, reporting ofprotocols and the planning, conduct and reporting of updates

Julian Higgins1, Toby Lasserson2, Jackie Chandler3, David Tovey4, James Thomas5, Ella Flemyng2, Rachel Churchill6

1 Professor of Evidence Synthesis, University of Bristol, Bristol, UK2 Cochrane Editorial and Methods Department, Cochrane, London, UK3Evaluation Programme Manager, Wessex Academic Health Science Network, Southampton, UK4 Editor in Chief (2009-2019), Cochrane Library, Editorial and Methods Department5Professor of Social Research and Policy, University College London, London, UK6 Centre for Reviews and Dissemination, University of York, York, UK

These MECIR Standards present a guide to the conduct and reporting of Cochrane Intervention Reviews. Each set ofStandards includes links to Cochrane Training resources, the Cochrane Handbook for Systematic Reviews of Interventions (the Handbook) and other available resources.

This online version will be kept up to date. A PDF of each section can be generated. All substantive changes will be noted here.

MECIR Standards link to the most up-to-date version of the Handbook chapters.Where links to external resources are included Cochrane Interactive Learning is referred to as 'CIL'.We welcome your feedback on MECIR, or if you have any general queries related to the MECIR Standards, pleasecontact [email protected].

Key points and introductionKey points:

The MECIR Standards represent a true collaborative effort across our community.They are an essential part of Cochrane’s quality assurance strategy.The MECIR Standards represent a living programme of work and will be adapted over time as methods andexpectations change.

Ensuring that Cochrane Reviews represent the highest possible quality is critical if they are to inform decision making in clinicalpractice and health policy. Methodological Expectations of Cochrane Intervention Reviews (MECIR) are Standards that shouldguide the conduct and reporting of Cochrane Intervention Reviews. They are drawn from the Cochrane Handbook for SystematicReviews of Interventions (the ‘Handbook’). The development of the Standards has been a collaborative effort over several years,involving review authors, editors and methodologists from all corners of our community. In this document we present a complete setof Standards for intervention reviews.

Development and consultationWe established working groups to develop minimum standards based on early proposals and groundwork by many groups andindividuals within Cochrane. We agreed the need to identify methodological expectations for Cochrane protocols, reviews andupdates of reviews on the effects of interventions that could be implemented across Cochrane. Six Working Groups covered sixcore methodological aspects of Cochrane Intervention Reviews:

developing a question and deciding the scope of the review,

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http://community.cochrane.org/sites/default/files/uploads/MECIR-February-2021.pdf

searching for studies, selecting studies and collecting data, assessing risk of bias in studies, analysing data and undertaking meta-analyses, interpretation and presenting results.

For each of these areas, we set out to identify the following in respect of intervention reviews: A. essential minimum standards (must do);B. desirable standards (should do);C. common errors (should not do);D. fatal flaws (must not do) and identification of any important methodological uncertainties.

The existing Standards address A and B. At least one methodologist and one Co-ordinating Editor (clinical specialist) jointly ledeach working group. We sought to ensure that groups reflected divergent views and had access to appropriate expertise. We co-opted other people from across Cochrane as necessary to ensure co-ordination and consistency of approach (training andknowledge translation). From an initial draft set of Standards based primarily on the 2011 version of the Handbook, we consultedwidely throughout Cochrane, after which the MECIR co-ordinating author team collated responses to produce the full original set ofStandards. We have updated the Standards regularly since their first publication. They now reflect the guidance available in themost up-to-date publicly available version of the Handbook.

Implementation of the StandardsThe Methodological Expectations for Cochrane Intervention Review (MECIR) are the Standards that each Cochrane InterventionReview should meet. Review authors and Cochrane Review Groups are expected to adhere or oversee adherence to theseStandards across different stages of the review process: protocols, reviews and updates.

All Standards are qualified with the status of ‘mandatory’ or ‘highly desirable’. Mandatory Standards should always be met unlessan appropriate justification for not doing so can be provided. Highly desirable Standards should generally be implemented butjustification for not implementing them is unnecessary. We introduce each set of Standards with key points and where necessaryadditional explanatory notes. The MECIR conduct Standards (C1-C75) are included in the Cochrane Handbook for SystematicReviews of Interventions.

Since the MECIR Standards were launched in 2011, technology has developed and changed how reviews are being produced. Thedevelopment of web-based platforms such as Covidence, EPPI-Reviewer, and GRADEpro GDT, as well as tools supporting semi-automation, have changed the way that systematic reviews are produced. Whilst we can expect technology to develop and helpimprove efficiency in production of Cochrane Reviews, these Standards remain a fundamental element of the preparation andquality assurance of individual Cochrane Intervention Reviews.

The MECIR Standards represent a considerable amount of work from many people within the Cochrane community. The core teamof Julian Higgins, Rachel Churchill, Toby Lasserson, my predecessor, David Tovey, and Jackie Chandler have made substantialcontributions to the process. I am delighted to welcome James Thomas and Ella Flemyng to an expanded team of authors tocoincide with the launch of version 6 of the Handbook.

We continue to welcome feedback from all of you who are responsible for delivering the Standards, and hope that they are useful toyou in producing and maintaining high quality, relevant reviews that can guide decision makers throughout the world, in pursuit ofbetter health.

Karla Soares-WeiserEditor in ChiefThe Cochrane Library

AcknowledgementsAcknowledgements

We thank the following working group leads and contributors for their early development of the Standards: Doug Altman, Mohammed Ansari (Methods lead), Sally Bell-Syer, Patrick Bossuyt, Deborah Caldwell, Christopher Cates, Rachel Churchill

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(Co-ordinating Editors (Co-Eds) lead, Co-ordinating team), Mike Clarke (Co-Eds co-lead), Jan Clarkson (Co-Eds co-lead), Philippa Davies, Marina Davoli (Co-Eds lead), Ruth Foxlee, Chantelle Garritty, Davina Ghersi (Co-Eds co-lead), JulieGlanville (Methods co-lead), Peter Herbison, Julian Higgins (Co-ordinating team), Sophie Hill (Co-Eds lead), Toby Lasserson(Co-ordinating team), Edith Leclercq, Carol Lefebvre (Methods co-lead), Jessie McGowan, Rachel Marshall, Ruth Mitchell,Donal O’Mathuna, Anna Noel-Storr, Georgia Salanti (Methods lead), Doug Salzwedel, Margaret Sampson, Jelena Savovic, Holger Schünemann (Methods lead), Ian Shemilt, Nandi Siegfried Jonathan Sterne (Methods lead), Britta Tendal(Methods lead), David Tovey (Co-ordinating team), Peter Tugwell, Lucy Turner, Claire Vale, Julia Walters, Helen Worthington(Co-Eds lead), and Janelle Yorke. We also thank all those Cochrane members of Review Groups, Methods Groups, Fields,Centres and Training who responded in some detail to MECIR Standards consultations, allowing us to improve these Standards toensure relevance and comprehension.

Versions and changes to MECIRProcess for updating MECIR

For details on when and how updates to MECIR are made, please see here.

Updates pending for the next version (August 2021)

C52 and C56 will be merged into one assessing risk of bias Conduct Standard (C52: Assess the risk of bias for each studyresult contributing to an outcome in the ‘Summary of findings’ table. For randomized trials, the RoB 2 tool should be used,involving judgements and support for those judgements across a series of domains of bias, as described in the Handbook);C57 to become C56, C58 to become C57, C59 to become C58, C60 to become C59 and there will no longer be a C60MECIR Conduct Standard

Version February 2021 (click here for the PDF version)

C56: Highly desirable -changed to- C56: MandatoryR106: ‘Declarations of interest’, updated to reflect Cochrane’s new Conflict of interest policy.

Version March 2020 (click here for the PDF version)

During February and March 2020 edits were made to the PR, R, U and UR Standards in MECIR to update referencing tothe new Handbook (version 6). All changes are reflected at the bottom of each page.PR14: Define in advance which outcomes are primary outcomes and which are secondary outcomes. -changed to- Define inadvance outcomes that are critical to the review, and any additional important outcomes.PR27: Assess the risk of bias for each included study. For randomized trials, the Cochrane 'Risk of bias' tool should beused, involving judgements and supports for those judgements across a series of domains of bias, as described in Chapter8 of the Handbook (version 5 or later). -changed to- Assess the risk of bias in at least one specific result for each included study. For randomized trials, the RoB 2 tool should beused, involving judgements and support for those judgements across a series of domains of bias, as described in Handbook (version 6).PR28: If the Risk of Bias 2 tool (see Handbook (version 6) Chapter 8) is to be used, state whether interest will be in theeffect of assignment to intervention or the effect of adhering to intervention, and explain how results will be selected to beassessed for risk of bias (i.e. for which outcome domains, outcome measures, time points and analyses). ADDEDPR35: according to summary risk of bias, or restricted to studies at low risk of bias. -changed to- according to summary riskof bias, restricted to studies at low risk of bias or restricted to low-and-some-concerns of risk of bias.R32: Define in advance which outcomes are primary outcomes and which are secondary outcomes. -changed to- Define inadvance outcomes that are critical to the review, and any additional important outcomes.R45: Assess the risk of bias for each included study. For randomized trials, the Cochrane 'Risk of bias' tool should be used,involving judgements and supports for those judgements across a series of domains of bias, as described in Chapter 8 ofthe Handbook (version 5 or later). -changed to- Assess the risk of bias in at least one specific result for each included study.For randomized trials, the RoB 2 tool should be used, involving judgements and support for those judgements across aseries of domains of bias, as described in Handbook version 6.R53: according to summary risk of bias, or restricted to studies at low risk of bias. -changed to- according to summary riskof bias, restricted to studies at low risk of bias or restricted to low-and-some-concerns of risk of bias.R55: (Include a ‘Summary of Findings’ table according to recommendations described in Chapter 10 of the CochraneHandbook (version 5 or later). Specifically:include results for one population group (with few exceptions);indicate the intervention and the comparison intervention;

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include seven or fewer patient-important outcomes;describe the outcomes (e.g. scale, scores, follow-up);indicate the number of participants and studies for each outcome;present at least one baseline risk for each dichotomous outcome (e.g. study population or median/medium risk) andbaseline scores for continuous outcomes (if appropriate);summarize the intervention effect (if appropriate); andinclude a measure of the certainty of the body of evidence) -changed to- Justify and document all assessments of the certainty of the body of evidence (for example downgrading or upgrading ifusing GRADE). R55: MECIR conduct standard 76 (Use the five GRADE considerations (study limitations, consistency of effect,imprecision, indirectness and publication bias) to assess the certainty of the body of evidence for each outcome, and todraw conclusions about the certainty of evidence within the text of the review.) [PRISMA item 12] - changed to- MECIR conduct standard 74: Use the five GRADE considerations (risk of bias, consistency of effect, imprecision,indirectness and publication bias) to assess the certainty of the body of evidence for each outcome, and to drawconclusions about the certainty of evidence within the text of the review. R56: to complete a PRISMA type flow chart -changed to- to be able to complete a flow diagramR73: Present a ‘Risk of bias’ table for each included study -changed to- Present at least one ‘Risk of bias’ table for eachstudy that is included in a synthesisR73: The ‘Risk of bias’ table in RevMan should be used, this is an extension of the table of ‘Characteristics of includedstudies’. -changed to- ‘Risk of bias’ presentation tools in RevMan should be used wherever possible.R73: Assess the risk of bias for each included study. For randomized trials, the Cochrane 'Risk of bias' tool should be used,involving judgements and supports for those judgements across a series of domains of bias, as described in Chapter 8 ofthe Handbook (version 5 or later) -changed to- Assess the risk of bias in at least one specific result for each included study.For randomized trials, the RoB 2 tool should be used, involving judgements and support for those judgements across aseries of domains of bias, as described in Handbook (version 6).R74: Summarize the risk of bias -changed to- Present an overall risk of bias assessment R76: the heading hierarchy -changed to- any heading hierarchyR76: in RevMan5 ADDEDR76: This standard will not be required when using the study-centric data structure of RevMan Web. ADDEDR101: Consider the potential impact of reporting biases -changed to- Consider the potential impact of non-reporting biasesU9: For randomized trials, they must be assessed using a currently accepted version of the Cochrane ‘Risk of bias’ tool.The separation of performance bias and detection bias in the evaluation of blinding is highly desirable. -changed to- If theprevious version used the original risk of bias tool to assess randomised trials, consider whether or not to switch to the Riskof Bias 2 tool (see Handbook (version 6) Chapter 8), including how many randomised trials were assessed in the previousversion, how many new studies are expected for inclusion in the update, how well it was implemented in the previousversion and whether it is feasible to switch.

Version October 2019

(Version October 2019 is an archived version of MECIR, provided for historical reference. Please see the current version ofMECIR here)

Version July 2019 - changed to- Version October 2019Updates made to MECIR authors' affiliationsLinks to version 6 of the Cochrane Handbook for Systematic Reviews of Interventions added to all relevant standards(Conduct Standards C1-C75)Links to the Cochrane Editorial and Publishing Policy Resource updatedJames Thomas and Ella Flemyng added as co-authorsEdits made to the MECIR Standards ‘Key points and introduction’ page (see ‘Section info’ on the page for details).Edits made to the ‘Development and consultation’ page (see ‘Section info’ on the page for details)New ‘Implementation of the standards’ section written by Karla Soares-Weiser (see ‘Section info’ on the page for details)Edits made to the ‘Key points and introduction’ pages for each of the four sections (see ‘Section info’ on the conduct,reporting of protocols, reporting and updates pages for details)Added a new ‘Translations of the MECIR Standards’ sectionCitation to the MECIR Manual as a whole and each section updated to reflect Version October 2019U11, column 2: quality -changed to- certainty (x2)UR5, column 3: quality -changed to- certaintyUR7, column 3: quality -changed to- certaintyPR39 column 2 and 3: quality -changed to- certainty (x4)

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PR40 column 3: quality -changed to- certaintyR12, column 3: quality -changed to- certaintyR55: column 2 and 3: quality -changed to- certainty (x4)R96: column 3: quality -changed to- certainty R98: column 3: quality -changed to- certainty (x2)R99 column 2 and 3: quality -changed to- certainty (x5)R100, column 3: Quality -changed to- Certainty

Version July 2019

Version July 2019 is an archived version of MECIR, provided for historical reference. Please see the current version of MECIR here.

Version 1.07 - changed to- Version July 2019Previous pages titled ‘Latest substantive changes’ and ‘Versions’ have been merged into one page titled ‘Versions andchanges to MECIR’ Citation to the MECIR Manual as a whole and each section updated to reflect version July 2019C1: See Handbook 2.3.2, 2.3.4, 17.2, 20.2.2 -changed to- See Handbook (version 6), Section 2.1C2: See Handbook 5.1.1 -changed to- See Handbook (version 6), Section 2.3C3: See Handbook 5.4.3, 14.1.1, 14.3 -changed to- See Handbook (version 6) Section 2.1C4: added: See Handbook (version 6), Section 2.4C5: Handbook 5.2 -changed to- Handbook (version 6), Section 3.2.1C6: Handbook 5.2 -changed to- Handbook (version 6), Section 3.2.1C7: Handbook 5.3 -changed to- Handbook (version 6), Section 3.2.2C8: Handbook 5.1.2 -changed to- Handbook (version 6), Section 3.2.4.1C9: Handbook 5.5, 13.2.2 -changed to- Handbook (version 6), Section 3.3C10: Handbook 5.5, 13.1.3 -changed to- Handbook (version 6), Section 3.3.1C11: Handbook 13.1.2 -changed to- Handbook (version 6), Section 3.3C12: Handbook 10.3.2 -changed to- Handbook (version 6), Section 3.4C13: Handbook 5.2, 5.7 -changed to- Handbook (version 6), Section 3.2.1C14, column 2: Define in advance which outcomes are primary outcomes and which are secondary outcomes. -changed to-Define in advance outcomes that are critical to the review, and any additional important outcomes. C14, column 3: The primary outcomes -changed to- The critical outcomesC14, column 3: It is important to identify up to seven outcomes from the primary and secondary outcomes that will form thebasis of the GRADE assessment. -changed to- Additional important outcomes may also be specified. Up to seven criticaland important outcomes will form the basis of the GRADE assessment and summarized in the review's abstract and othersummary formats, although the review may measure more than seven outcomes.C14, column 4: Handbook 5.4.2 -changed to- Handbook (version 6), Section 3.2.4.1C15, column 2: that are important -changed to- that are critical or importantC15, column 3: that are important -changed to- that are critical or importantC15, column 3 new text: Any outcomes that would not be described as critical or important can be left out of the review.C15, column 4: Handbook 5.4.2 -changed to- Handbook (version 6), Section 3.2.4.1C16, column 4: Handbook 5.4.1 -changed to- Handbook (version 6), Section 3.2.4.1C19, column 4: Handbook 6.3, 6.4 -changed to- Handbook (version 6), Section 1.5; 4.3.1.1C20, column 3: 'Risk of bias' -changed to- 'risk of bias'C20, column 4: Handbook 8.3 -changed to- Handbook (version 6), Section 1.5 C21, column 4:Handbook 9.1.2 -changed to- Handbook (version 6), Section 1.5 C22, column 4:Handbook 9.6.5 -changed to- Handbook (version 6), Section 1.5 C23, column 4:Handbook 11.5 -changed to- Handbook (version 6), Section 1.5 C24 column 3: Supplementary searches should be performed as described in sections 6.3.2 and 6.3.3 of the Handbook.-changed to- DELETEDC24: BLANK -changed to- See Handbook (version 6) Section 4.3.1.1C25: Handbook 6.2.1.4, 6.2.1.5 -changed to- Handbook (version 6), Section 4.3.1.4C26: Handbook 13.3; 14.5; 15.3; 20.3.2.1 -changed to- Handbook (version 6), Section 4.4.1C27: Handbook 6.2.3.1, 6.2.3.2, 6.2.3.3 -changed to- Handbook (version 6), Section 4.4.3C28: Handbook 6.2.1.7, 6.2.1.8, 6.2. 2-changed to- Handbook (version 6), Section 4.3.5C29: Handbook 6.2.2.5 -changed to- Handbook (version 6), Section 4.3.5C30: Handbook 6.2.2.5 -changed to- Handbook (version 6), Section 4.3.5C31: Handbook 6.2.3-changed to- Handbook (version 6), Section 4.3.2C32: Handbook 6.4.2, 6.4.4, 6.4.7-changed to- Handbook (version 6), Section 4.4.2C33: Handbook 6.4.5, 6.4.6, 6.4.8 -changed to- Handbook (version 6), Section 4.4.4

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C34: Handbook 6.4.11, 6.4.2; 13.3.1.2; 14.5.2; 15.3.1; 17.5; 20.3.2.1 -changed to- Handbook (version 6), Section 4.4.7C35: Handbook 6.4.9 -changed to- Handbook (version 6), Section 4.4.5C36: Handbook 6.6.1 -changed to- Handbook (version 6), Section 4.5C37: BLANK -changed to- Handbook (version 6), Section 4.4.10C38: BLANK -changed to- Handbook (version 6), Section 4.4.10C39 column 4: Handbook 7.2.4 -changed to- Handbook (version 6), Section 4.6.4C40 column 4: Handbook 5.4.1 -changed to- Handbook (version 6), Section 4.6.3C41 column 3: A PRISMA type flow diagram and a table of ‘Characteristics of excluded studies’ will need to be completedin the final review. -changed to- DELETEDC41 column 4: Handbook 6.6.1; 11.2.1 -changed to- Handbook (version 6), Section 4.6.4C42 column 4: Handbook 7.2.1, 7.2.2, 7.6.4 -changed to- Handbook (version 6), Section 4.6.2; 5.2.1C43 column 2: that has been -changed towhich has beenC43 column 3: Piloting the form within the review team using a sample of included studies is highly desirable -changed to-Piloting the form within the review team is highly desirable. C43 column 4: Handbook 7.5 -changed to- Handbook (version 6), Section 5.4.1C44 column 3: Details of funding source for each study and the declarations of interest for the primary investigators shouldalso be collected during this process. TiDieR (Hoffman 2014) will assist selection of which characteristics of interventionsshould be sought. -changed to- DELETEDC44 column 4: Handbook 7.3; 11.2 -changed to- Handbook (version 6), Section 5.3.1C45 column 3: not a mandatory standard for study characteristics. -changed to- not a mandatory standard for the former.C45 column 4: Handbook 7.6.2, 7.6.5 -changed to- Handbook (version 6), Section 5.5.2C46 column 4: Handbook 7.6.2 -changed to- Handbook (version 6), Section 5.5.2C47 column 4: Handbook 7.7 -changed to- Handbook (version 6), Section 5.3.6C48 column 4: Handbook 6.4.10 -changed to- Handbook (version 6), Section 4.4.6; 5.2C49 column 3: Risk of bias -changed to- risk of biasC49 column 4: Handbook 7.4.2 -changed to- Handbook (version 6), Section 5.2.3C50 title: Choosing intervention groups in multi-arm studies -changed to- Choosing interventions in multi-arm studiesC50 column 2: include in the review only the intervention and control groups that meet -changed to- include in the reviewonly the interventions that meetC50 column 3: intervention groups (x2) -changed to- interventions (x2)C50 column 4: Handbook 16.5.2 -changed to- Handbook (version 6), Section 5.3.6C52 column 3: Recommendations for assessing bias in randomized studies included in Cochrane Reviews are now wellestablished. -changed to- DELETEDC52 column 3: as described in this Handbook -changed toas described in Handbook version 6C52 column 4: See Handbook version 6 (Chapter 8) -changed to- See Handbook (version 6), Section 7.1.2; Chapter 8C53 column 2: risk of bias tool -changed to- risk-of-bias-toolC53 column 3: the risk of bias assessment -changed to- the risk-of-bias assessmentC53 column 4: See Handbook 8.3.4 -changed to- See Handbook (version 6), Section 7.3.2; Chapter 8C54 column 2: risk of bias tables -changed to- risk-of bias tablesC54 column 3: Items that are judged to be at an unclear risk of bias but are without accompanying information supportingthe judgment appear as empty cells in the graphical plots based on the ‘Risk of bias’ tool in the published review. -changedto- DELETEDC54 column 4: Handbook 8.5.2 -changed to- Handbook (version 6), Section 7.3.2; Chapter 8C55 column 2: risk of bias judgement -changed to- risk-of-bias judgementC54 column 3: judgments -changed to- judgementsC55 column 4: Handbook 8.5.2 -changed to- Handbook (version 6), Section 7.3.2; Chapter 8C56 column 4: Handbook 8.5.1, 8.11.2, 8.12.2 -changed to- Handbook (version 6), Section 7.3.2; Chapter 8C57 title: Summarizing risk of bias assessments changed to- Summarizing risk-of-bias assessmentsC57 column 4: Handbook 8.5.1, 8.13.2 -changed to- Handbook (version 6), Section 7.5; Chapter 8C58 column 4: Handbook 8.7 -changed to- Handbook (version 6), Section 7.6.1; Chapter 8C59 column 4: Handbook version 6 (Chapter 8) -changed to- Handbook (version 6), Section 7.6.1; Chapter 8C60 column 3: “notable concern of conflicts of interest” -changed to- “notable concern about conflicts of interest”C60 column 4: Handbook 8.8.1 -changed to- Handbook (version 6), Section 7.8.6; Chapter 8C61 column 4: Handbook 9.2.3.2 -changed to- BLANKC62 column 4: See Handbook 9.1.4 -changed to- BLANKC63 column 4: See Handbook 9.5.2 -changed to- See Handbook (version 6), Section 10.10.2C64 column 3: Risk of bias tool -changed to- 'risk-of-bias' toolC64 column 4: See Handbook 16.2 -changed to- See Handbook (version 6), Section 10.12.1C65 column 4 See Handbook 9.4.5.3 -changed to- See Handbook (version 6), Section 10.5.3C66 column 3: and using multiple treatments meta-analysis. -changed to- and using network meta-analysis.C66 column 4: See Handbook 7.7.3.8, 16.5.4 -changed to- See Handbook (version 6), Section 6.2.9 and Chapter 11.

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C67 column 4:See Handbook 9.6.3.1 -changed to- See Handbook (version 6), Section 10.11.3.1C68 column 4: See Handbook 9.6.5.2 -changed to- See Handbook (version 6), Section 10.11.5.2C69 column 4: See Handbook 9.5.4 -changed to- See Handbook (version 6), Section 10.10.3C70 column 3: of the study, i.e., to give it (x2) -changed to- of the study, that is, to give it (x2)C70 column 4: see Handbook 9.3, 16.3, 16.4 -changed to- See Handbook (version 6), Section 6.2.1C71 column 4: see Handbook 9.7 -changed to- See Handbook (version 6), Section 10.14C72 column 2: Interpret a statistically non-significant P value (e.g. larger than 0.05) as a finding of uncertainty unlessconfidence intervals are sufficiently narrow to rule out an important magnitude of effect. -changed to- (Do not describeresults as statistically significant or non-significant. Interpret the confidence intervals and their width.) Focus interpretationof results on estimates of effect and their confidence intervals, avoiding use of a distinction between “statistically significant”and “statistically non-significant".C72 column 4: See Handbook 12.4.2, 12.7.4 -changed to- See Handbook (version 6), Section 15.3.1C73 column 4: See Handbook 10.1, 10.2 -changed to- See Handbook (version 6), Section 13.4C74 column 2 title: Assessing the quality -changed to- Assessing the certaintyC74 column 2: quality of the body of evidence -changed to -certainty of the body of evidenceC74 column 2: quality of evidence -changed to- certainty of evidenceC74 column 3: quality of the body of evidence -changed to -certainty of the body of evidenceC74 column 4: See Handbook 12.2 -changed to- See Handbook (version 6) Section 14.2.1C75 column 2 title: quality of the body of evidence -changed to -certainty of the body of evidenceC75 column 2: quality of the body of evidence -changed to -certainty of the body of evidenceC75 column 4: See Handbook 12.2.1 -changed to- See Handbook (version 6) Section 14.2.1

Version 1.07, 2018

Version 1.07 is an archived version of MECIR, provided for historical reference. Please see the current version of MECIR here.

C56: "assess RoB due to lack of blinding......" replaced with NEW standard "Ensuring results of outcomes included in SoFare assessed for RoB......."C57: "RoB due to incomplete outcome data...." replaced with "Summarizing RoB assessments...."C58: "Summarizing RoB assessments...." replaced with "Addressing RoB in the synthesis...."C59: "Addressing RoB in the synthesis...." replaced with "Incorporating assessments of RoB...."C60: "Incorporating assessments of RoB...." replaced with NEW standard "Addressing CoI in included trials....."

Version 1.06

C73: Standard changed to: Consider the potential impact of non-reporting biases on the results of the review or the meta-analysis it contains. Rationale and elaboration changed to: There is overwhelming evidence of non-reporting biases ofvarious types. These can be addressed at various points of the review. A thorough search, and attempts to obtainunpublished results, might minimize the risk. Analyses of the results of included studies, for example using funnel plots, cansometimes help determine the possible extent of the problem, as can attempts to identify study protocols, which should be aroutine feature of Cochrane Reviews.C24: Standard changed from “Planning the search” to “Searching general bibliographic databases and CENTRAL”C41: Standard changed to: “Document the selection process in sufficient detail to be able to complete a flow diagram and atable of ‘Characteristics of excluded studies’. Change elaboration to read: “A PRISMA type flow diagram and a table of‘Characteristics of excluded studies’ will need to be completed in the final review……..”R56: Standard changed to: Provide information on the flow of studies…………., ideally using a PRISMA type flowdiagram……………..individual studies”.UR4: Elaboration changed to: “Provide information on the flow of studies into the updated review, ideally using a PRISMAtype flow diagram.”R98: Status changed to mandatory – Mandating SoF tables.R102: Changed elaboration to: “When formulating implications for practice base conclusions only on findings from thesynthesis (quantitative or narrative) of studies included in the review. The conclusions of the review should convey theessence of the synthesis of included studies, without selective reporting of particular findings on the basis of the result, andwithout drawing on data that were not systematically compiled and evaluated as part of the review.”

Version 1.05

C48: Upgraded from 'highly desirable' to 'mandatory'.

Version 1.04

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R55: New Standard inserted. There is subsequent renumbering of all Standards in section up to R108.(23/01/2018)C28: Changed from 'mandatory' to 'highly desirable'.(23/01/18)Links to Cochrane Interactive Learning modules have been added where needed.

MECIR Booklet 2016

MECIR Booklet Version 2, December 2013

MECIR Booklet Version 2, September 2013

MECIR Booklet 2012

How to cite the MECIR StandardsHiggins JPT, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E, Churchill R. Methodological Expectations of CochraneIntervention Reviews. Cochrane: London, Version February 2021.

Standards for the CONDUCT of new Cochrane Intervention Reviews (C1-C75) Key points and introductionKey points:

The conduct Standards should be consulted during preparation of the protocol for a Cochrane InterventionReview.They describe the methods that should be implemented throughout the review process.Few specific methods are mandatory, one notable exception being the Cochrane tool for assessing risk of biaswhen randomized trials are included in the review.

The MECIR Standards for conduct of a Cochrane Intervention Review provide expectations for the general methodologicalapproach to be followed from designing the review up to interpreting the findings at the end. They should be consulted particularlywhen preparing the protocol for the review. The protocol describes the review question, the criteria for considering studies for thereview, and the methods that will be followed to identify, appraise, summarize and synthesize the studies. Cochrane led the way inmaking protocols available to readers of the Cochrane Library. They ensure transparency in how reviews are prepared and allowthe planned methods to be critiqued. Specification of the review question (through setting the review’s objectives) and the criteriafor including studies are critical to the success of the review and the first two sections of the Standards address these tasks. Thefollowing section addresses selection of the outcomes of interest, an important aspect that should be prespecified carefully to avoidthe need for post hoc decisions that could be influenced by the data.

The remaining Standards address the detailed methodology that will be followed during the review, covering the search for studies,selection of studies into the review, data collection, risk of bias assessment, synthesis (including any meta-analysis approaches),and overall assessment of the evidence. With few exceptions (such as use of the Cochrane Risk of Bias 2 tool for randomizedtrials), the precise methods to be used are not prescribed, For example, authors are free to use any meta-analysis method, althoughthere is a potential convenience to both authors and readers if those implemented in Review Manager (RevMan) software areused.

Julian HigginsProfessor of Evidence SynthesisUniversity of Bristol

Developing the protocol of the review (C1-C23)Cochrane Training resource: writing a protocol and common errors and best practice: writing review protocols

Cochrane Interactive Learning (CIL): module 2 - writing the review protocol

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Setting the research question to inform the scope of the review (C1-C4)

Setting the research question(s) to inform the scope of the review

Cochrane Training resource: defining the review question

Cochrane Interactive Learning (CIL): module 1 - introduction to conducting systematic reviews

Standard Rationale and elaboration ResourcesC1 Formulating review questions Mandatory Ensure that the review question

and particularly the outcomes ofinterest, address issues thatare important to review userssuch as consumers, healthprofessionals and policymakers.

Cochrane Reviews areintended to support clinicalpractice and policy, not justscientific curiosity. The needsof consumers play a central rolein Cochrane Reviews and theycan play an important role indefining the review question.Qualitative research, i.e.studies that explore theexperience of those involved inproviding and receivinginterventions, and studiesevaluating factors that shapethe implementation ofinterventions, might be used inthe same way.

See Handbook Section 2.1

C2 Predefining objectives Mandatory Define in advance the

objectives of the review,including participants,interventions, comparators andoutcomes (PICO).

Objectives give the reviewfocus and must be clear beforeappropriate eligibility criteriacan be developed. If the reviewwill address multipleinterventions, clarity is requiredon how these will be addressed(e.g. summarized separately,combined or explicitlycompared).


C3 Considering potential adverseeffects

Mandatory

Consider any importantpotential adverse effects of theintervention(s) and ensure thatthey are addressed.

It is important that adverseeffects are addressed in orderto avoid one-sided summariesof the evidence. At a minimum,the review will need to highlightthe extent to which potentialadverse effects have beenevaluated in any includedstudies. Sometimes data onadverse effects are bestobtained from non-randomizedstudies, or qualitative researchstudies. This does not meanhowever that all reviews mustinclude non-randomizedstudies.


Cochrane Training resource: adverse effects

C4 Considering equity and specific Highly desirable

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populations Consider in advance whether

issues of equity and relevanceof evidence to specificpopulations are important to thereview, and plan for appropriatemethods to address them ifthey are. Attention should bepaid to the relevance of thereview question to populationssuch as low-socioeconomicgroups, low- or middle-incomeregions, women, children andolder people.

Where possible reviews shouldinclude explicit descriptions ofthe effect of the interventionsnot only upon the wholepopulation, but also on thedisadvantaged, and/or theability of the interventions toreduce socioeconomicinequalities in health, and topromote use of theinterventions to the community.


Cochrane Training resources: equity issues and PRISMA-E2012

Setting eligibility criteria for including studies in the review (C5-C13)

Setting the eligibility criteria for including studies in the review


Cochrane Interactive Learning (CIL): module 2 - writing the review protocol

Standard Rationale and elaboration ResourcesC5 Predefining unambiguous

criteria for participantsMandatory

Define in advance the eligibilitycriteria for participants in thestudies.

Predefined, unambiguouseligibility criteria are afundamental prerequisite for asystematic review. The criteriafor considering types of peopleincluded in studies in a reviewshould be sufficiently broad toencompass the likely diversityof studies, but sufficientlynarrow to ensure that ameaningful answer can beobtained when studies areconsidered in aggregate.Considerations when specifyingparticipants include setting,diagnosis or definition ofcondition and demographicfactors. Any restrictions tostudy populations must bebased on a sound rationale,since it is important thatCochrane Reviews are widelyrelevant.

See Handbook Section 3.2.1

C6 Predefining a strategy forstudies with a subset of eligibleparticipants

Highly desirable

Define in advance how studiesthat include only a subset ofrelevant participants will beaddressed.

Sometimes a study includessome ‘eligible’ participants andsome ‘ineligible’ participants,for example when an age cut-


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off is used in the review’seligibility criteria. If data fromthe eligible participants cannotbe retrieved, a mechanism fordealing with this situationshould be prespecified.

C7 Predefining unambiguouscriteria for interventions andcomparators

Mandatory

Define in advance the eligibleinterventions and theinterventions against whichthese can be compared in theincluded studies.

Predefined, unambiguouseligibility criteria are afundamental prerequisite for asystematic review. Specification of comparatorinterventions requires particularclarity: are the experimentalinterventions to be comparedwith an inactive controlintervention (e.g. placebo, notreatment, standard care, or awaiting list control), or with anactive control intervention (e.g.a different variant of the sameintervention, a different drug, adifferent kind of therapy)? Anyrestrictions on interventions andcomparators, for example,regarding delivery, dose,duration, intensity,cointerventions and features ofcomplex interventions shouldalso be predefined andexplained.


C8 Clarifying role of outcomes Mandatory Clarify in advance whether

outcomes listed under 'Criteriafor considering studies for thisreview' are used as criteria forincluding studies (rather thanas a list of the outcomes ofinterest within whicheverstudies are included).

Outcome measures should notalways form part of the criteriafor including studies in a review.However, some reviews dolegitimately restrict eligibility tospecific outcomes. Forexample, the same interventionmay be studied in the samepopulation for differentpurposes (e.g. hormonereplacement therapy, oraspirin); or a review mayaddress specifically theadverse effects of anintervention used for severalconditions. If authors doexclude studies on the basis ofoutcomes, care should be takento ascertain that relevantoutcomes are not availablebecause they have not beenmeasured rather than simplynot reported.

See Handbook Section 3.2.4.1

C9 Predefining study designs Mandatory Define in advance the eligibility

criteria for study designs in aPredefined, unambiguouseligibility criteria are a


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clear and unambiguous way,with a focus on features of astudy's design rather thandesign labels.

fundamental prerequisite for asystematic review. This isparticularly important when non-randomized studies areconsidered. Some labelscommonly used to define studydesigns can be ambiguous. Forexample a ‘double blind’ studymay not make it clear who wasblinded; a ‘case control’ studymay be nested within a cohort,or be undertaken in a cross-sectional manner; or a‘prospective’ study may haveonly some features defined orundertaken prospectively.

C10 Including randomized trials Mandatory Include randomized trials as

eligible for inclusion in thereview, if it is feasible toconduct them to evaluateinterventions and outcomes ofinterest.

Randomized trials are the beststudy design for evaluating theefficacy of interventions. If it isfeasible to conduct them toevaluate questions that arebeing addressed by the review,they must be consideredeligible for the review. However,appropriate exclusion criteriamay be put in place, forexample regarding length offollow-up.


C11 Justifying choice of studydesigns

Mandatory

Justify the choice of eligiblestudy designs.

It might be difficult to addresssome interventions or someoutcomes in randomized trials.Authors should be able to justifywhy they have chosen either torestrict the review torandomized trials or to includenon-randomized studies. Theparticular study designsincluded should be justified withregard to appropriateness tothe review question and withregard to potential for bias.


C12 Excluding studies based onpublication status

Mandatory

Include studies irrespective oftheir publication status, unlessexclusion is explicitly justified.

Obtaining and including datafrom unpublished studies(including grey literature) canreduce the effects of publicationbias. However, the unpublishedstudies that can be located maybe an unrepresentative sampleof all unpublished studies.


C13 Changing eligibility criteria Mandatory Justify any changes to eligibility

criteria or outcomes studied. InFollowing prespecified eligibilitycriteria is a fundamental


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particular, post hoc decisionsabout inclusion or exclusion ofstudies should keep faith withthe objectives of the reviewrather than with arbitrary rules.

attribute of a systematic review.However, unanticipated issuesmay arise. Review authorsshould make sensible post hocdecisions about exclusion ofstudies, and these should bedocumented in the review,possibly accompanied bysensitivity analyses. Changes tothe protocol must not be madeon the basis of the findings ofthe studies or the synthesis, asthis can introduce bias.

Selecting outcomes to be addressed for studies included in the review (C14-C18)

Selecting outcomes to be addressed for studies included in the review


Cochrane Interactive Learning: module 2 - writing the review protocol

Standard Rationale and elaboration ResourcesC14 Predefining outcome domains Mandatory Define in advance outcomes

that are critical to the review,and any additional importantoutcomes.

Full specification of theoutcomes includesconsideration of outcomedomains (e.g. quality of life) andoutcome measures (e.g.SF-36). Predefinition ofoutcome reduces the risk ofselective outcome reporting.The critical outcomes shouldbe as few as possible andshould normally reflect at leastone potential benefit and atleast one potential area ofharm. It is expected that thereview should be able tosynthesize these outcomes ifeligible studies are identified,and that the conclusions of thereview will be based largely onthe effects of the interventionson these outcomes. Additionalimportant outcomes may alsobe specified. Up to sevencritical and important outcomeswill form the basis of theGRADE assessment andsummarized in the review'sabstract and other summaryformats, although the reviewmay measure more than sevenoutcomes.


Planning GRADE andSummary of Findings tables

C15 Choosing outcomes Mandatory

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Choose only outcomes that arecritical or important to users ofthe review such as healthcareconsumers, healthprofessionals and policymakers.

Cochrane Reviews areintended to support clinicalpractice and policy, and shouldaddress outcomes that arecritical or important toconsumers. These should bespecified at protocol stage.Where available, establishedsets of core outcomes shouldbe used. Patient-reportedoutcomes should be includedwhere possible. It is alsoimportant to judge whetherevidence of resource use andcosts might be an importantcomponent of decisions toadopt the intervention oralternative managementstrategies around the world.Large numbers of outcomes,while sometimes necessary,can make reviews unfocussed,unmanageable for the user, andprone to selective outcomereporting bias. Biochemical,interim and process outcomesshould be considered wherethey are important to decisionmakers. Any outcomes thatwould not be described ascritical or important can be leftout of the review.


C16 Predefining outcome measures Highly desirable Define in advance details of

what will constitute acceptableoutcome measures (e.g.diagnostic criteria, scales,composite outcomes).

Having decided what outcomesare of interest to the review,authors should clarifyacceptable ways in which theseoutcomes can be measured. Itmay be difficult, however, topredefine adverse effects.


C17 Predefining choices frommultiple outcome measures

Highly desirable

Define in advance how outcomemeasures will be selected whenthere are several possiblemeasures (e.g. multipledefinitions, assessors orscales).

Prespecification guards againstselective outcome reporting,and allows users to confirm thatchoices were not overlyinfluenced by the results. Apredefined hierarchy ofoutcomes measures may behelpful. It may be difficult,however, to predefine adverseeffects. A rationale should beprovided for the choice ofoutcome measure.

C18 Predefining time points ofinterest

Highly desirable

Define in advance the timing ofoutcome measurement.

Prespecification guards againstselective outcome reporting,and allows users to confirm thatchoices were not overly

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influenced by the results.Authors may consider whetherall time frames or only selectedtime points will be included inthe review. These decisionsshould be based on outcomesimportant for making healthcaredecisions. One strategy tomake use of the available datacould be to group time pointsinto prespecified intervals torepresent ‘short-term’, ‘medium-term’ and ‘long-term’ outcomesand to take no more than onefrom each interval from eachstudy for any particularoutcome.

Planning the review methods at protocol stage (C19-C23)

Planning the review methods at protocol stage

Standard Rationale and elaboration ResourcesC19 Planning the search Mandatory Plan in advance the methods to

be used for identifying studies.Design searches to capture asmany studies as possible thatmeet the eligibility criteria,ensuring that relevant timeperiods and sources arecovered and not restricted bylanguage or publication status.

Searches should be motivateddirectly by the eligibility criteriafor the review, and it isimportant that all types ofeligible studies are consideredwhen planning the search. Ifsearches are restricted bypublication status or bylanguage of publication, there isa possibility of publication bias,or language bias (whereby thelanguage of publication isselected in a way that dependson the findings of the study), orboth. Removing languagerestrictions in English languagedatabases is not a goodsubstitute for searching non-English language journals anddatabases.

See Handbook Section 1.5; 4.3.1.1

Cochrane Training resource: searching studies

CIL: module 3 - searching forstudies

C20 Planning the assessment ofrisk of bias in included studies

Mandatory

Plan in advance the methods tobe used for assessing risk ofbias in included studies,including the tool(s) to be used,how the tool(s) will beimplemented, and the criteriaused to assign studies, forexample, to judgements of lowrisk, high risk and unclear riskof bias.

Predefining the methods andcriteria for assessing risk ofbias is important since analysisor interpretation of the reviewfindings may be affected by thejudgements made during thisprocess. For randomized trials,use of the Cochrane ‘risk ofbias’ tool is Mandatory, so it issufficient (and easiest) simply


Cochrane Training resource: risk of bias

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to refer to the definitions of lowrisk, unclear risk and high riskof bias provided in the Handbook.

C21 Planning the synthesis ofresults

Mandatory

Plan in advance the methods tobe used to synthesize theresults of the included studies,including whether a quantitativesynthesis is planned, howheterogeneity will be assessed,choice of effect measure (e.g.odds ratio, risk ratio, riskdifference or other fordichotomous outcomes), andmethods for meta-analysis (e.g.inverse variance or MantelHaenszel, fixed-effect orrandom-effects model).

Predefining the synthesismethods, particularly thestatistical methods, isimportant, since analysis orinterpretation of the reviewfindings may be affected by thejudgements made during thisprocess.


Cochrane Training resources: meta-analysis; dichotomousoutcomes; continuousoutcomes and heterogeneity

CIL: module 6 - analysing thedata

C22 Planning sub-group analyses Mandatory Predefine potential effect

modifiers (e.g. for subgroupanalyses) at the protocol stage;restrict these in number, andprovide rationale for each.

Prespecification reduces therisk that large numbers ofundirected subgroup analyseswill lead to spuriousexplanations of heterogeneity.


Cochrane Training resource: heterogeneity


C23 Planning the GRADEassessment and ‘Summary offindings’ table

Mandatory

Plan in advance the methods tobe used for assessing thequality of the body of evidence,and summarizing the findings ofthe review.

Methods for assessing thequality of evidence for the mostimportant outcomes in thereview need to be prespecified.In ‘Summary of findings’ tablesthe most important feature is topredefine the choice ofoutcomes in order to guardagainst selective presentationof results in the review. Thetable should include theessential outcomes for decisionmaking (typically up to seven),which generally should notinclude surrogate or interimoutcomes. The choice ofoutcomes should not be basedon any anticipated or observedmagnitude of effect, or becausethey are likely to have beenaddressed in the studies to bereviewed.


Cochrane Training resource: evaluating evidence

CIL: module 7 - interpreting thefindings


Performing the review (C24-C75)

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Searching for studies (C24-C38)

Searching for studies

Cochrane Training resource: searching for studies

Cochrane Interactive Learning (CIL): module 3 - searching for studies

Standard Rationale and elaboration ResourcesC24 Searching general

bibliographic databases andCENTRAL

Mandatory

Search the Cochrane ReviewGroup's (CRG’s) SpecializedRegister (internally, e.g. via theCochrane Register of Studies,or externally via CENTRAL).Ensure that CENTRAL,MEDLINE (e.g. via PubMed)and Embase (if Embase isavailable to either the CRG orthe review author), have beensearched (either for the reviewor for the Review Group’sSpecialized Register).

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible. The minimumdatabases to be covered arethe CRG’s Specialized Register(if it exists and was designed tosupport reviews in this way),CENTRAL, MEDLINE andEmbase (if Embase is availableto either the CRG or the reviewauthor). Expertise may berequired to avoid unnecessaryduplication of effort. Some, butnot all, reports of eligiblestudies from MEDLINE,Embase and the CRGs’Specialized Registers arealready included in CENTRAL. .


Cochrane Training resource: Register of Studies andRevMan

C25 Searching specialistbibliographic databases

Highly desirable

Search appropriate national,regional and subject-specificbibliographic databases.

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible. Databases relevant tothe review topic should becovered (e.g. CINAHL fornursing-related topics,PsycINFO for psychologicalinterventions), and regionaldatabases (e.g. LILACS)should be considered.


C26 Searching for different types ofevidence

Mandatory

If the review has specificeligibility criteria around studydesign to address adverseeffects, economic issues orqualitative research questions,undertake searches to addressthem.

Sometimes different searcheswill be conducted for differenttypes of evidence, such as fornon-randomized studies foraddressing adverse effects, orfor economic evaluationstudies.


Cochrane Training resource: searching for adverse effects

C27 Searching trials registers Mandatory

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Search trials registers andrepositories of results, whererelevant to the topic, throughClinicalTrials.gov, the WHOInternational Clinical TrialsRegistry Platform (ICTRP)portal and other sources asappropriate.

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible. AlthoughClinicalTrials.gov is included asone of the registers within theWHO ICTRP portal, it isrecommended that bothClinicalTrials.gov and theICTRP portal are searchedseparately due to additionalfeatures in ClinicalTrials.gov.


C28 Searching for grey literature Highly desirable Search relevant grey literature

sources such as reports,dissertations, theses,databases and databases ofconference abstracts.

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible.


C29 Searching within other reviews Highly desirable Search within previous reviews

on the same topic.Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible.


C30 Searching reference lists Mandatory Check reference lists in

included studies and anyrelevant systematic reviewsidentified.

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible.


C31 Searching by contactingrelevant individuals andorganizations

Highly desirable

Contact relevant individualsand organizations forinformation about unpublishedor ongoing studies.

Searches for studies should beas extensive as possible inorder to reduce the risk ofpublication bias and to identifyas much relevant evidence aspossible. It is important toidentify ongoing studies, so thatthese can be assessed forpossible inclusion when areview is updated.


C32 Structuring search strategiesfor bibliographic databases

Mandatory

Inform the structure of searchstrategies in bibliographicdatabases around the mainconcepts of the review, usingappropriate elements fromPICO and study design. In

Inappropriate or inadequatesearch strategies may fail toidentify records that areincluded in bibliographicdatabases. Expertise may needto be sought, in particular from


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structuring the search,maximize sensitivity whilststriving for reasonableprecision. Ensure correct use ofthe ‘AND’ and ‘OR’ operators.

the CRG’s InformationSpecialist. The structure of asearch strategy should bebased on the main conceptsbeing examined in a review. Ingeneral databases, such asMEDLINE, a search strategy toidentify studies for a CochraneReview will typically have threesets of terms: 1) terms tosearch for the health conditionof interest, i.e. the population;2) terms to search for theintervention(s) evaluated; and3) terms to search for the typesof study design to be included(typically a ‘filter’ forrandomized trials). There areexceptions, however. Forinstance, for reviews ofcomplex interventions, it maybe necessary to search only forthe population or theintervention. Within eachconcept, terms are joinedtogether with the Boolean ‘OR’operator, and the concepts arecombined with the Boolean‘AND’ operator. The ‘NOT’operator should be avoidedwhere possible to avoid thedanger of inadvertentlyremoving records that arerelevant from the search set.

C33 Developing search strategiesfor bibliographic databases

Mandatory

Identify appropriate controlledvocabulary (e.g. MeSH,Emtree, including 'exploded'terms) and free-text terms(considering, for example,spelling variants, synonyms,acronyms, truncation andproximity operators).

Inappropriate or inadequatesearch strategies may fail toidentify records that areincluded in bibliographicdatabases. Search strategiesneed to be customized for eachdatabase. It is important thatMeSH terms are ‘exploded’wherever appropriate, in ordernot to miss relevant articles.The same principle applies toEmtree when searchingEmbase and also to a numberof other databases. Thecontrolled vocabulary searchterms for MEDLINE andEmbase are not identical, andneither is the approach toindexing. In order to be ascomprehensive as possible, it isnecessary to include a widerange of free-text terms foreach of the concepts selected.This might include the use oftruncation and wildcards.


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Developing a search strategy isan iterative process in whichthe terms that are used aremodified, based on what hasalready been retrieved.

C34 Using search filters Highly desirable Use specially designed and

tested search filters whereappropriate including theCochrane Highly SensitiveSearch Strategies foridentifying randomized trials inMEDLINE, but do not use filtersin pre-filtered databases e.g. donot use a randomized trial filterin CENTRAL or a systematicreview filter in DARE.

Inappropriate or inadequatesearch strategies may fail toidentify records that areincluded in bibliographicdatabases. Search filtersshould be used with caution.They should be assessed notonly for the reliability of theirdevelopment and reportedperformance, but also for theircurrent accuracy, relevanceand effectiveness given thefrequent interface and indexingchanges affecting databases.


C35 Restricting database searches Mandatory Justify the use of any

restrictions in the searchstrategy on publication dateand publication format.

Date restrictions in the searchshould only be used when thereare date restrictions in theeligibility criteria for studies.They should be applied only if itis known that relevant studiescould only have been reportedduring a specific time period,for example if the interventionwas only available after acertain time point. Searches forupdates to reviews mightnaturally be restricted by dateof entry into the database(rather than date of publication)to avoid duplication of effort.Publication format restrictions(e.g. exclusion of letters) shouldgenerally not be used inCochrane Reviews, since anyinformation about an eligiblestudy may be of value.


C36 Documenting the searchprocess

Mandatory

Document the search processin enough detail to ensure that itcan be reported correctly in thereview.

The search process (includingthe sources searched, when, bywhom, and using which terms)needs to be documented inenough detail throughout theprocess to ensure that it can bereported correctly in the review,to the extent that all thesearches of all the databasesare reproducible.


C37 Rerunning searches Mandatory Rerun or update searches for

all relevant databases within 12months before publication of

The published review should beas up to date as possible. Thesearch must be rerun close to


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the review or review update,and screen the results forpotentially eligible studies.

publication, if the initial searchdate is more than 12 months(preferably six months) from theintended publication date, andthe results screened forpotentially eligible studies.Ideally the studies should beincorporated fully in the review.If not, then the potentiallyeligible studies will need to bereported, at a minimum as areference under ‘Studiesawaiting classification’ (or‘Ongoing studies’ if they havenot yet completed).

C38 Incorporating findings fromrerun searches

Highly desirable

Fully incorporate any studiesidentified in the rerun or updateof the search within 12 monthsbefore publication of the reviewor review update.

The published review should beas up to date as possible. Afterthe rerun of the search, thedecision whether to incorporateany new studies fully into thereview will need to be balancedagainst the delay in publication.


Selecting studies to include in the review (C39-C42)

Selecting studies to include in the review

Cochrane Training resources: selecting studies and Covidence webinar (online tool for review production)

Cochrane Interactive Learning (CIL): module 4 - selecting studies and collecting data

Standard Rationale and elaboration ResourcesC39 Making inclusion decisions Mandatory Use (at least) two people

working independently todetermine whether each studymeets the eligibility criteria, anddefine in advance the processfor resolving disagreements.

Duplicating the study selectionprocess reduces both the riskof making mistakes and thepossibility that selection isinfluenced by a single person’sbiases. The inclusion decisionsshould be based on the fulltexts of potentially eligiblestudies when possible, usuallyafter an initial screen of titlesand abstracts. It is desirable,but not mandatory, that twopeople undertake this initialscreening, workingindependently.


C40 Excluding studies withoutuseable data

Mandatory

Include studies in the reviewirrespective of whethermeasured outcome data arereported in a ‘usable’ way.

Systematic reviews typicallyshould seek to include allrelevant participants who havebeen included in eligible study


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designs of the relevantinterventions and had theoutcomes of interest measured.Reviews must not excludestudies solely on the basis of reporting of the outcome data,since this may introduce biasdue to selective outcomereporting and risk underminingthe systematic review process.While such studies cannot beincluded in meta-analyses, theimplications of their omissionshould be considered. Note thatstudies may legitimately beexcluded because outcomeswere not measured.Furthermore, issues may bedifferent for adverse effectsoutcomes, since the pool ofstudies may be much largerand it can be difficult to assesswhether such outcomes weremeasured.

C41 Documenting decisions aboutrecords identified

Mandatory

Document the selectionprocess in sufficient detail to beable to complete a flow diagramand a table of ‘Characteristicsof excluded studies’.

Decisions should therefore bedocumented for all recordsidentified by the search.Numbers of records aresufficient for exclusions basedon initial screening of titles andabstracts. Broadcategorizations are sufficient forrecords classed as potentiallyeligible during an initial screen.Studies listed in the table of‘Characteristics of excludedstudies’ should be those that auser might reasonably expect tofind in the review. At least oneexplicit reason for theirexclusion must be documented.Authors will need to decide foreach review when to maprecords to studies (if multiplerecords refer to one study).Lists of included and excludedstudies must be based onstudies rather than records.


C42 Collating multiple reports Mandatory Collate multiple reports of the

same study, so that each study,rather than each report, is theunit of interest in the review.

It is wrong to consider multiplereports of the same study as ifthey are multiple studies.Secondary reports of a studyshould not be discarded,however, since they maycontain valuable informationabout the design and conduct.Review authors must choose

See Handbook Sections 4.6.2; 5.2.1

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and justify which report to useas a source for study results.

Collecting data from included studies (C43-C51)

Collecting data from included studies

Cochrane Training resources: collecting data and Covidence webinar (online tool for review production)

Cochrane Interactive Learning (CIL): module 4 - selecting studies and collecting data

Standard Rationale and elaboration ResourcesC43 Using data collection forms Mandatory Use a data collection form

which has been piloted.Review authors often havedifferent backgrounds and levelof systematic reviewexperience. Using a datacollection form ensures someconsistency in the process ofdata extraction, and isnecessary for comparing dataextracted in duplicate. Thecompleted data collection formsshould be available to the CRGon request. Piloting the formwithin the review team is highlydesirable. At a minimum, thedata collection form (or a veryclose variant of it) must havebeen assessed for usability.


C44 Describing studies Mandatory Collect characteristics of the

included studies in sufficientdetail to populate a table of‘Characteristics of includedstudies’.

Basic characteristics of eachstudy will need to be presentedas part of the review, includingdetails of participants,interventions and comparators,outcomes and study design.


C45 Extracting study characteristicsin duplicate

Highly desirable

Use (at least) two peopleworking independently toextract study characteristicsfrom reports of each study, anddefine in advance the processfor resolving disagreements.

Duplicating the data extractionprocess reduces both the riskof making mistakes and thepossibility that data selection isinfluenced by a single person’sbiases. Dual data extractionmay be less important for studycharacteristics than it is foroutcome data, so it is not amandatory standard for theformer.


C46 Extracting outcome data induplicate

Mandatory

Use (at least) two peopleworking independently toextract outcome data fromreports of each study, anddefine in advance the process

Duplicating the data extractionprocess reduces both the riskof making mistakes and thepossibility that data selection isinfluenced by a single person’s


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for resolving disagreements. biases. Dual data extraction isparticularly important foroutcome data, which feeddirectly into syntheses of theevidence, and hence to theconclusions of the review.

C47 Making maximal use of data Mandatory Collect and utilize the most

detailed numerical data thatmight facilitate similar analysesof included studies. Where 2×2tables or means and standarddeviations are not available,this might include effectestimates (e.g. odds ratios,regression coefficients),confidence intervals, teststatistics (e.g. t, F, Z, Chi2) or Pvalues, or even data forindividual participants.

Data entry into RevMan iseasiest when 2×2 tables arereported for dichotomousoutcomes, and when meansand standard deviations arepresented for continuousoutcomes. Sometimes thesestatistics are not reported butsome manipulations of thereported data can be performedto obtain them. For instance,2×2 tables can often be derivedfrom sample sizes andpercentages, while standarddeviations can often becomputed using confidenceintervals or P values.Furthermore, the inverse-variance data entry format canbe used even if the detaileddata required for dichotomousor continuous data are notavailable, for instance if onlyodds ratios and theirconfidence intervals arepresented. The RevMancalculator facilitates many ofthese manipulations.


Cochrane Training resources: dichotomous outcomes and continuous outcomes

C48 Examining errata Mandatory* Examine any relevant retraction

statements and errata forinformation.

Some studies may have beenfound to be fraudulent or mayhave been retracted sincepublication for other reasons.Errata can reveal importantlimitations, or even fatal flaws,in included studies. All of thesemay lead to the potentialexclusion of a study from areview or meta-analysis. Careshould be taken to ensure thatthis information is retrieved inall database searches bydownloading the appropriatefields, together with the citationdata.

See Handbook Section 4.4.6; 5.2

C49 Obtaining unpublished data Highly desirable Seek key unpublished

information that is missing fromreports of included studies.

Contacting study authors toobtain or confirm data makesthe review more complete,


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potentially enhances precisionand reduces the impact ofreporting biases. Missinginformation includes details toinform ‘risk of bias’assessments, details ofinterventions and outcomes,and study results (includingbreakdowns of results byimportant subgroups).

C50 Choosing interventions in multi-arm studies

Mandatory

If a study is included with morethan two intervention arms,include in the review only theinterventions that meet theeligibility criteria.

There is no point includingirrelevant interventions in thereview. Authors, however,should make it clear in the‘Table of characteristics ofincluded studies’ that theseinterventions were present inthe study.


Cochrane Training resource: non-standard data and studydesign

C51 Checking accuracy of numericdata in the review

Mandatory

Compare magnitude anddirection of effects reported bystudies with how they arepresented in the review, takingaccount of legitimatedifferences.

This is a reasonablystraightforward way for authorsto check a number of potentialproblems, includingtypographical errors in studies’reports, accuracy of datacollection and manipulation,and data entry into RevMan. For example, the direction of astandardized mean differencemay accidentally be wrong inthe review. A basic check is toensure the same qualitativefindings (e.g. direction of effectand statistical significance)between the data as presentedin the review and the data asavailable from the originalstudy. Results in forest plotsshould agree with data in theoriginal report (point estimateand confidence interval) if thesame effect measure andstatistical model is used.

Cochrane Trainingresource: common errors

Assessing risk of bias in included studies (C52-C60)Cochrane Training resources: assessing RoB and RoB 2.0 webinar

Cochrane Interactive Learning (CIL): module 5 - introduction to study quality and risk of bias

Standard Rationale and elaboration ResourcesC52 Assessing risk of bias

Anupdate to this Standard ispending

Mandatory

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Assess the risk of bias in at

least one specific result foreach included study. Forrandomized trials, the RoB 2tool should be used, involvingjudgements and support forthose judgements across aseries of domains of bias, asdescribed in Handbook version6.

The risk of bias in at least onespecific result for everyincluded study must beexplicitly considered todetermine the extent to whichits findings can be believed,noting that risks of bias mightvary by result. The RoB 2 tool –as described in Handbookversion 6– must be used for allrandomized trials in newreviews. This does not preventother tools being used.

See Handbook Section 7.1.2; Chapter 8

C53 Assessing risk of bias induplicate

Mandatory

Use (at least) two peopleworking independently to applythe risk-of-bias tool to eachincluded study, and define inadvance the process forresolving disagreements.

Duplicating the risk-of-biasassessment reduces both therisk of making mistakes and thepossibility that assessments areinfluenced by a single person’sbiases.


C54 Supporting judgements of riskof bias

Mandatory

Justify judgements of risk ofbias (high, low and someconcerns) and provide thisinformation in the risk-of-biastables (as ‘Support forjudgement’).

Providing support for thejudgement makes the processtransparent.


C55 Providing sources ofinformation for risk of biasassessments

Mandatory

Collect the source ofinformation for each risk of biasjudgement (e.g. quotation,summary of information from atrial report, correspondencewith investigator etc.). Wherejudgements are based onassumptions made on the basisof information provided outsidepublicly available documents,this should be stated.

Readers, editors and refereesshould have the opportunity tosee for themselves from wheresupports for judgements havebeen obtained.


C56 Ensuring results of outcomesincluded in ‘Summary offindings’ tables are assessedfor risk of bias

An updateto this Standard is pending

Mandatory

Ensure that assessments of riskof bias cover the outcomesincluded in the ‘Summary offindings’ table.

It may not be feasible to assessthe risk of bias in every singleresult available across theincluded studies, particularly ifa large number of studies and


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results are available. Reviewauthor should strive to assessrisk of bias in the results ofoutcomes that are mostimportant to patients. Suchoutcomes will typically beincluded in ‘Summary offindings’ tables, which presentthe findings of seven or fewerpatient-important outcomes.

C57 Summarizing risk-of-biasassessments.

Highly desirable

Summarize the risk of bias foreach key outcome for eachstudy

This reinforces the link betweenthe characteristics of the studydesign and their possibleimpact on the results of thestudy and is an importantprerequisite for the GRADEapproach to assessing thecertainty of the body ofevidence.

See Handbook Section 7.5; Chapter 8

C58 Addressing risk of bias in thesynthesis.

Highly desirable

Address risk of bias in thesynthesis (whether quantitativeor non-quantitative). Forexample, present analysesstratified according to summaryrisk of bias, or restricted tostudies at low risk of bias.

Review authors should considerhow study biases affect results.This is useful in determining thestrength of conclusions andhow future research should bedesigned and conducted.


C59 Incorporating assessments ofrisk of bias.

Mandatory

If randomized trials have beenassessed using one or moretools in addition to the RoB 2tool, use the RoB 2 tool as theprimary assessment of bias forinterpreting results, choosingthe primary analysis, anddrawing conclusions.

For consistency of approachacross Cochrane InterventionReviews, the RoB 2 tool shouldtake precedence when two ormore tools are used forassessing risk of bias inrandomized trials. The RoB 2tool also feeds directly into theGRADE approach forassessing the certainty of thebody of evidence.


C60 Addressing conflicts of interestin included trials.

Highly desirable

Address conflict of interests inincluded trials, and reflect onpossible impact on: a)differences in study design; b)risk of bias in trial result, and c)risk of bias in synthesis result

Review authors should considerassessing whether they judge atrial to be of “notable concernabout conflicts of interest”. Thisassessment is useful forexploration of possibleheterogeneity between trials(e.g. in a subgroup analysis),and for reflection on relevantmechanisms for how conflict ofinterest may have biased trialresults and synthesis results.Concerns about conflicts ofinterest can be reported in the


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‘Characteristics of includedstudies’ table.

Synthesizing the results of included studies (C61-C73)

Synthesizing the results of included studies

Cochrane Interactive Learning (CIL): module 6 - analysing the data

Standard Rationale and elaboration ResourcesC61 Combining different scales Mandatory If studies are combined with

different scales, ensure thathigher scores for continuousoutcomes all have the samemeaning for any particularoutcome; explain the directionof interpretation; and reportwhen directions are reversed.

Sometimes scales have higherscores that reflect a ‘better’outcome and sometimes lowerscores reflect ‘better’ outcome.Meaningless (and misleading)results arise when effectestimates with opposite clinicalmeanings are combined.

Cochrane Trainingresource: analysing continuousoutcomes

C62 Ensuring meta-analyses aremeaningful

Mandatory

Undertake (or display) a meta-analysis only if participants,interventions, comparisons andoutcomes are judged to besufficiently similar to ensure ananswer that is clinicallymeaningful.

Meta-analyses of very diversestudies can be misleading, forexample where studies usedifferent forms of control.Clinical diversity does notindicate necessarily that a meta-analysis should not beperformed. However, authorsmust be clear about theunderlying question that allstudies are addressing.

Cochrane Training resources: intro to meta-analysis and exploring heterogeneity

C63 Assessing statisticalheterogeneity

Mandatory

Assess the presence andextent of between-studyvariation when undertaking ameta-analysis.

The presence of heterogeneityaffects the extent to whichgeneralizable conclusions canbe formed. It is important toidentify heterogeneity in casethere is sufficient information toexplain it and offer new insights.Authors should recognize thatthere is much uncertainty inmeasures such as I2 and Tau2

when there are few studies.Thus, use of simple thresholdsto diagnose heterogeneityshould be avoided.


Cochrane Training resource: exploring heterogeneity

C64 Addressing missing outcomedata

Highly desirable

Consider the implications of Incomplete outcome data can See Handbook Section 10.12.1

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missing outcome data fromindividual participants (due tolosses to follow-up orexclusions from analysis).

introduce bias. In mostcircumstances, authors shouldfollow the principles of intention-to-treat analyses as far aspossible (this may not beappropriate for adverse effectsor if trying to demonstrateequivalence). Risk of bias dueto incomplete outcome data isaddressed in the Cochrane'riskof-bias' tool. However,statistical analyses and carefulinterpretation of results areadditional ways in which theissue can be addressed byreview authors. Imputationmethods can be considered(accompanied by, or in the formof, sensitivity analyses).

Cochrane Training resources: assessing RoB included studiesand RoB 2.0 webinar

C65 Addressing skewed data Highly desirable Consider the possibility and

implications of skewed datawhen analysing continuousoutcomes.

Skewed data are sometimesnot summarized usefully bymeans and standarddeviations. While statisticalmethods are approximatelyvalid for large sample sizes,skewed outcome data can leadto misleading results whenstudies are small.


Cochrane Training resource: analysing continuous outcomes

C66 Addressing studies with morethan two groups

Mandatory

If multi-arm studies areincluded, analyse multipleintervention groups in anappropriate way that avoidsarbitrary omission of relevantgroups and double-counting ofparticipants.

Excluding relevant groupsdecreases precision and double-counting increases precisionspuriously; both areinappropriate and unnecessary.Alternative strategies includecombining intervention groups,separating comparisons intodifferent forest plots and usingnetwork meta-analysis.

See Handbook Section 6.2.9and Chapter 11.

Cochrane Training resource: analysing non-standard data &study designs

C67 Comparing subgroups Mandatory If subgroup analyses are to be

compared, and there arejudged to be sufficient studiesto do this meaningfully, use aformal statistical test tocompare them.

Concluding that there is adifference in effect in differentsubgroups on the basis ofdifferences in the level ofstatistical significance withinsubgroups can be verymisleading.

See Handbook Section10.11.3.1

Cochrane Trainingresources: exploringheterogeneity and commoninterpretation errors

C68 Interpreting subgroup analyses Mandatory If subgroup analyses are

conducted, follow the subgroupanalysis plan specified in theprotocol without undueemphasis on particular findings.

Selective reporting, or over-interpretation, of particularsubgroups or particularsubgroup analyses should beavoided. This is a problemespecially when multiplesubgroup analyses areperformed. This does notpreclude the use of sensible


Cochrane Training resources: exploring heterogeneity and common interpretation errors

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and honest post hoc subgroupanalyses.

C69 Considering statistical

heterogeneity when interpretingthe results

Mandatory

Take into account anystatistical heterogeneity wheninterpreting the results,particularly when there isvariation in the direction ofeffect.

The presence of heterogeneityaffects the extent to whichgeneralizable conclusions canbe formed. If a fixed-effectanalysis is used, the confidenceintervals ignore the extent ofheterogeneity. If a random-effects analysis is used, theresult pertains to the meaneffect across studies. In bothcases, the implications ofnotable heterogeneity should beaddressed. It may be possibleto understand the reasons forthe heterogeneity if there aresufficient studies.



C70 Addressing non-standarddesigns

Mandatory

Consider the impact on theanalysis of clustering, matchingor other non-standard designfeatures of the included studies

Cluster-randomized trials, cross-over trials, studies involvingmeasurements on multiple bodyparts, and other designs needto be addressed specifically,since a naive analysis mightunderestimate or overestimatethe precision of the study.Failure to account for clusteringis likely to overestimate theprecision of the study,that is, togive it confidence intervals thatare too narrow and a weightthat is too large. Failure toaccount for correlation is likelyto underestimate the precisionof the study, that is, to give itconfidence intervals that are toowide and a weight that is toosmall.


Cochrane Training resource: non-standard study designs

C71 Sensitivity analysis Highly desirable Use sensitivity analyses to

assess the robustness ofresults, such as the impact ofnotable assumptions, imputeddata, borderline decisions andstudies at high risk of bias.

It is important to be aware whenresults are robust, since thestrength of the conclusion maybe strengthened or weakened.



C72 Interpreting results Mandatory Focus interpretation of results

on estimates of effect and theirconfidence intervals, avoidinguse of a distinction between“statistically significant” and“statistically non-significant".

Authors commonly mistake alack of evidence of effect asevidence of a lack of effect.


Cochrane Training resource: common interpretation errors

CIL: module 7 - interpreting the

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findingsC73 Investigating risk of bias due to

missing resultsHighly desirable

Consider the potential impact ofnon-reporting biases on theresults of the review or the meta-analyses it contains.

There is overwhelmingevidence of non-reportingbiases of various types. Thesecan be addressed at variouspoints in the review. A thoroughsearch, and attempts to obtainunpublished results, mightminimize the risk. Analyses ofthe results of included studies,for example using funnel plots,can sometimes help determinethe possible extent of theproblem, as can attempts toidentify study protocols, whichshould be a routine feature ofCochrane Reviews.


Cochrane Training resources: small study effects & reportingbiases


Assessing the quality of evidence and summarizing the findings (C74-C75)

Assessing the quality of evidence and summarizing the findings

Cochrane Training resource: GRADE approach to evaluating evidence quality

Cochrane Interactive Learning: module 7 - interpreting the findings

Standard Rationale and elaboration ResourcesC74 Assessing the certainty of the

body of evidenceMandatory

Use the five GRADEconsiderations (risk of bias,consistency of effect,imprecision, indirectness andpublication bias) to assess thecertainty of the body ofevidence for each outcome,and to draw conclusions aboutthe certainty of evidence withinthe text of the review.

GRADE is the most widely usedapproach for summarizingconfidence in effects ofinterventions by outcomeacross studies. It is preferableto use the online GRADEprotool, and to use it as describedin the help system of thesoftware. This should help toensure that author teams areaccessing the same informationto inform their judgments.Ideally, two people workingindependently should assessthe certainty of the body ofevidence and reach aconsensus view on anydowngrading decisions. Thefive GRADE considerationsshould be addressedirrespective of whether thereview includes a ‘Summary offindings’ table. It is helpful todraw on this information in theDiscussion, in the Authors’conclusions and to convey thecertainty in the evidence in the


Common issues in Summary ofFindings tables.

Planning GRADE andSummary of Findings tables.

Incorporating GRADE inCochrane Reviews.

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Abstract and Plain languagesummary.

C75 Justifying assessments of thecertainty of the body ofevidence

Mandatory

Justify and document allassessments of the certainty ofthe body of evidence (forexample downgrading orupgrading if using GRADE).

The adoption of a structuredapproach ensures transparencyin formulating an interpretationof the evidence, and the resultis more informative to the user.


Reference

Reference

Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. (2014) Better reporting of interventions: template forintervention description and replication (TIDieR) checklist and guide. BMJ 2014;348:g1687. doi: 10.1136/bmj.g1687

Citation

Citation of the Standards for the conduct of new Cochrane Intervention Reviews

Please cite this section as: Higgins JPT, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E, Churchill R. Standards for theconduct of new Cochrane Intervention Reviews. In: Higgins JPT, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E,Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, February 2021.

Standards for the REPORTING of PROTOCOLS of new Cochrane InterventionReviews (PR1-PR44) Key points and introductionKey points:

Publishing a protocol for a Cochrane Review establishes a public record of the review question and plannedmethods.Reporting clear definitions will help authors to adhere to a well formulated approach.Readers need to determine how far the review will address their own questions of interest.Changes to the review question or methods will need to be clearly described and justified in the full review.

Publishing the protocol for a Cochrane Systematic Review is a key milestone in the review process. As with any other form ofresearch, it finalizes the development of the research question and sets out the different methods that will be used to address it.

Preparing and publishing a clearly conceived and well-written protocol serves a number of purposes. Investment of effort in thedevelopment of the review question and methods and the definition of the different aspects of the eligibility criteria will providereview authors with a clear plan to guide implementation of methods and reporting the full review, reducing their reliance on posthoc decisions. Publishing the protocol gives readers access to the plan from which the review will develop. It also helps them tojudge how the eligibility criteria of the review, stated outcomes and planned methods will address the intended question of interest.

The protocol is a public record of the question of interest and the intended methods before results of the studies are fully known.This helps anyone who evaluates the review to judge how far it fulfills the original objectives. One of the key parts of the CochraneReview prepublication screening programme involves the comparison between the intended methods with those implementedduring the preparation of the review. It is crucial that review authors acknowledge and justify important differences betweenmethods stated in the protocol and those used to produce the review findings. This is key to supporting replication, and providesusers of the review with a sense of how far the review preserves the research question. Particularly important changes concern

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eligibility criteria, the definition or status of outcome measurements and methods relating to effect measures, data analysis andexploration of heterogeneity. Any changes that are made to these aspects of the review could potentially impact on the overallobjectives as well as the interpretation of the evidence summarized by the review.

On publication Cochrane systematic review protocols are automatically assigned a record on PROSPERO, the register of ongoingand completed systematic reviews. For more information see www.crd.york.ac.uk/PROSPERO/.

Toby LassersonDeputy Editor in ChiefCochrane Editorial and Methods Department

Reporting the review plan (PR1-PR44)

Reporting the review plan

Cochrane Training resources: writing the protocol and common errors in protocols


Title and Authors (PR1-PR2)

Title and Authors


Standard Rationale and elaboration ResourcesPR1 Format of title Highly desirable Follow the standard template

for a Cochrane Review title See Handbook Section II.1.3


PR2 Authors Mandatory List names and affiliations of all

authors See Handbook Section II.2

Cochrane Training resource: writing the protocol

Background (PR3-PR4)

Background

Cochrane Training resource: writing the protocol


Standard Rationale and elaboration ResourcesPR3 Background Mandatory Provide a concise description of

the condition or problemaddressed by the reviewquestion, a definition of the

Systematic reviews shouldhave a clearly defined and well-reasoned rationale that hasbeen developed in the context

See Handbook Section III.3.2

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intervention and how it mightwork, and why it is important todo the review. Include the fourstandard RevMan headingswhen writing the Background.

of existing knowledge. Outliningthe context of the reviewquestion is useful to readersand helps to establish keyuncertainties that the reviewintends to address.

Four standard headings areincluded in RevMan(‘Description of the condition’,‘Description of the intervention’,‘How the intervention mightwork’, and ‘Why it is importantto do this review’).

PR4 Background references Mandatory Back up all key supporting

statements with references.Claims or statements regardingaspects such as diseaseburden, morbidity, prevalenceand mechanisms of actionshould be substantiated and,where available, supported byevidence.

Objectives (PR5-PR8)

Objectives

Cochrane Training resource: defining the review question and writing the protocol


Standard Rationale and elaboration ResourcesPR5 Main objective Mandatory State the main objective, where

appropriate in a single concisesentence.

The primary objective of aCochrane Review should be toassess the effects of one ormore healthcare interventionson user-important outcomes,both intended and unintended.The objective should beexpressed in terms that relateto the population(s),intervention comparison(s) and,where appropriate to specifyexplicitly, the outcomes ofinterest (PICO). Review usersmay be patients, carers, policymakers, clinicians, practitionersor others.

The format should be: “Toassess the effects of [intervention or comparison] for[health problem] for/in [types ofpeople, disease or problemand setting if specified]”.

See Handbook Section III.3.2and Section 2.3

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MECIR conduct standard 2:Define in advance theobjectives of the review,including participants,interventions, comparators andoutcomes (PICO).

PR6 Secondary objectives Highly desirable State explicitly (as secondary

objectives) any specificquestions being addressed bythe review, such as thoserelating to particular participantgroups, interventioncomparisons or outcome.

The secondary objectivesshould be expressed in termsthat relate to the population(s),intervention comparison(s) and,where appropriate, outcomes ofinterest.

The format might be: “Toassess whether the effects of[intervention or comparison]differ according to [types ofpeople, intervention orcomparator characteristic,disease, problem, settingetc.]”.

Secondary objectives should bekept succinct, since they will bepublished in the front sheet ofthe review protocol on theCochrane Library.

MECIR conduct standard 4:Consider in advance whetherissues of equity and relevanceof evidence to specificpopulations are important to thereview, and plan for appropriatemethods to address them ifthey are. Attention should bepaid to the relevance of thereview question to populationssuch as low-socioeconomicgroups, low- or middle-incomeregions, women, children andolder people.

See Handbook Section III.3.2and Section 2.4

PR7 Economic evidence Mandatory If health economics evidence is

to be reviewed, state thisexplicitly in the Objectives (as asecondary objective).

The primary aim of a CochraneReview should be to assess theeffects of one or morehealthcare interventions onoutcomes, both intended andunintended, that are importantto review users. Theseoutcomes may includeeconomic outcomes. If healtheconomics evidence is beingreviewed as an integratedeconomics component, thisshould be stated as asecondary objective.


PR8 Qualitative research evidence Mandatory If qualitative research evidence If qualitative research evidence See Handbook Section 21.4

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is to be reviewed, state thisexplicitly in the Objectives (as asecondary objective).

is being included to ‘extend’ thereview, this should be stated asa secondary objective.

Criteria for considering studies for this review (PR9-PR16)

Criteria for considering studies for this review



Standard Rationale and elaboration ResourcesPR9 Eligibility criteria for types of

study: study designsMandatory

State eligible study designs,using key study characteristics,and provide a justification forthe choice.

It is not necessary to explainwhy randomized trials areeligible (if that is the case),although it may be important toexplain the eligibility or non-eligibility of other types of study.

Particular care may be neededto explain whether cross-overtrials and cluster-randomizedtrials are to be considered.

Study characteristics mightinclude details such as “withblind assessment of outcomes”or “with prospectiveidentification of participants”,rather than ambiguous labelssuch as “double blind” or“prospective study”.

If ‘conditional’ eligibility criteriaare used that are based onabsence of particular types ofevidence (e.g. when norandomized trials are found),this must be statedunambiguously (and detailedmethods for addressing allpotentially eligible studies willneed to be described).

MECIR conduct standard 9:Define in advance the eligibilitycriteria for study designs in aclear and unambiguous way,with a focus on features of astudy's design rather thandesign labels.

MECIR conduct standard 11:Justify the choice of eligible

See Handbook Section III.3.3.1and Section 3.3.3

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study designs.PR10 Eligibility criteria for types of

study: study reportsMandatory

If studies will be excluded onthe basis of publication statusor language of publication,explain and justify this.

Studies should be includedirrespective of their publicationstatus and language ofpublication, unless exclusion isexplicitly justified.

MECIR conduct standard 12:Include studies irrespective oftheir publication status, unlessexclusion is explicitly justified.

See Handbook SectionIII.3.3.1 and Section 3.4

PR11 Eligibility criteria for types ofparticipants

Mandatory

State eligibility criteria forparticipants, including anycriteria around location, setting,diagnoses or definition ofcondition and demographicfactors, and how studiesincluding subsets of relevantparticipants will be addressed.

MECIR conduct standard 5:Define in advance the eligibilitycriteria for participants in thestudies.

MECIR conduct standard6: Define in advance howstudies that include only asubset of relevant participantswill be addressed.


PR12 Eligibility criteria for types ofinterventions

Mandatory

State eligibility criteria forinterventions and comparators,including any criteria arounddelivery, dose, duration,intensity and cointerventions.Criteria for complexinterventions should be madeexplicit, e.g. by statingmandatory components.

Eligible interventions, andparticularly the comparators,must address the statedobjectives of the review. Forexample, inclusion of studieswith an active comparatorintervention is not consistentwith an objective to look only atwhether an experimentalintervention is effectivecompared with an inactivecontrol.

MECIR conduct standard 7:Define in advance the eligibleinterventions and theinterventions against whichthese can be compared in theincluded studies.


PR13 Role of outcomes Mandatory Be explicit about the role of

outcomes in determiningeligibility of studies for thereview.

For most Cochrane Reviews ofrandomized trials of theintended effects ofinterventions, the aim should beto identify and include allrelevant participants who havebeen randomized to theintervention comparisons ofinterest. The extent to whichoutcome data are available forthese people can be affected bydecisions made by the trialists –

See Handbook Section III.3.3.1and Section 3.2.4.1

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i.e. there is a risk of selectiveoutcome reporting bias.

An important distinction shouldbe made between whetheroutcomes were measured, andwhether the measured outcomedata are available. Studiesshould not be excluded from areview solely because nooutcome data are available.However, on occasion it will beappropriate to include onlystudies that measuredparticular outcomes. Forexample, a review of a multi-component public healthintervention promoting healthylifestyle choices, focussing onreduction in smokingprevalence, might legitimatelyexclude studies that do notmeasure smoking rates. Often itis difficult to know whetherunreported outcomes weremeasured, so it is generallyappropriate to include allstudies irrespective of whetheroutcomes are reported.

MECIR conduct standard 8:Clarify in advance whetheroutcomes listed under 'Criteriafor considering studies for thisreview' are used as criteria forincluding studies (rather thanas a list of the outcomes ofinterest within whicheverstudies are included).

PR14 Outcome domains of interest Mandatory Define in advance outcomes

that are critical to the review,and any additional importantoutcomes.

Up to seven outcomes shouldbe prespecified for inclusion ina ‘Summary of findings’ table(see PR40); it may beconvenient to highlight themhere.

MECIR conduct standard 14:Define in advance outcomesthat are critical to the review,and any additional importantoutcomes.

Also MECIR conduct standards15–18

See Handbook Section III.3.3.1and Section 3.2.4.1


PR15 Outcome measures of interest Mandatory Define relevant outcome

measures and time points formeasurement, and anyhierarchy for choosing among

Explain how multiple variants ofoutcome measures (e.g.definitions, assessors, scales,time points) will be addressed.

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them.PR16 Minimally important difference Highly desirable Define minimally important

differences for key outcomemeasures.

To facilitate interpretation of thesize of effect of an intervention,it is important to understand thesize of difference that isimportant to review users.

Cochrane Training resource: analysing continuous outcomes


Search methods for identification of studies (PR17-PR21)

Search methods for identification of studies


Cochrane Interactive Learning: module 3 - searching for studies

Standard Rationale and elaboration ResourcesPR17 Search sources Mandatory List all sources that will be

searched, including: CRGspecialized register(s),CENTRAL, other databases,trials registers, websites andgrey literature. State whetherreference lists will be searchedand whether individuals ororganizations will be contacted.

MECIR conduct standard 19:Plan in advance the methods tobe used for identifying studies.Design searches to capture asmany studies as possible thatmeet the eligibility criteria,ensuring that relevant timeperiods and sources arecovered and not restricted bylanguage or publication status.

MECIR conduct standard 36:Document the search processin enough detail to ensure that itcan be reported correctly in thereview.


See Handbook SectionIII.3.3.2; 1.5; 4.3.1.1 and section 4.4.5

PR18 Search restrictions Mandatory Specify and justify any

restrictions to be placed on thesearch (e.g. time period orpublication format).

MECIR conduct standard 35:Justify the use of anyrestrictions in the searchstrategy on publication date orpublication format.

See Handbook SectionIII.3.3.2 and Section 4.4.5

PR19 Searches for different types ofevidence

Mandatory

Some reviews extend beyond afocus on the effects ofhealthcare interventions andaddress specific additionaltypes of evidence.

MECIR conduct standard 26: Ifthe review has specificeligibility criteria around studydesign to address adverseeffects, economic issues orqualitative research questions,undertake searches to addressthem.

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These are discussed in the Handbook (version 6) Chapters19, 20 and 21.

PR20 Search strategies forbibliographic databases

Mandatory

Present the complete searchstrategy (or strategies) to beimplemented for at least onedatabase in an Appendix,including any limits and filters tobe used.

The line-by-line search stringshould be presented to facilitatepeer review. Search strategiesthat are available elsewhere(e.g. standard methodologicalfilters, or strategies used topopulate a specialized register)may be referenced rather thanreproduced. Note that when thefull review is published, it ismandatory to report searchstrategies used for alldatabases.




PR21 Search strategies for othersources

Highly desirable

Report search terms that will beused to search any sourcesother than bibliographicdatabases (e.g. trials registers,the web).

Some of this information mightbe best placed in an Appendix.



Data collection and analysis (PR22-PR40)

Data collection and analysis

Standard Rationale and elaboration ResourcesPR22 Inclusion decisions Mandatory State how inclusion decisions

will be made (i.e. from searchresults to included studies),clarifying how many people willbe involved and whether theywill work independently.

MECIR conduct standard 39:Use (at least) two peopleworking independently todetermine whether each studymeets the eligibility criteria, anddefine in advance the processfor resolving disagreements.


Cochrane Training resource: selecting studies

CIL: module 4 - selectingstudies and collecting data

PR23 Data collection process Mandatory State how data will be extracted

from reports of includedMECIR conduct standard 43:Use a data collection form that

See Handbook SectionIII.3.3.3, Section 5.4.1 and

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studies, clarifying how manypeople will be involved (andwhether they will workindependently), and howdisagreements will be resolved.

has been piloted.

MECIR conduct standard 45:Use (at least) two peopleworking independently toextract study characteristicsfrom reports of each study, anddefine in advance the processfor resolving disagreements

Section 5.5.2

Cochrane Training resource: collecting data


PR24 Requests for data Highly desirable Describe what attempts will be

made to obtain or clarify datafrom individuals ororganizations.

MECIR conduct standard49: Seek key unpublishedinformation that is missing fromreports of included studies.

See Handbook SectionIII.3.3.3,and Section 5.2.3



PR25 Data items Mandatory State the types of information

that will be sought from reportsof included studies.

This information is a usefulbasis for the design of datacollection forms and alsoindicates what sort ofinformation about the includedstudies readers mightanticipate seeing in the full textof the review. Detailed lists arenot necessary. Instead, a broadoutline of the summaryinformation that authors mightcollect will suffice, for example:

“We will collect information onstudy design and setting,participant characteristics(including disease severity andage), study eligibility criteria,details of the intervention(s)given, the outcomes assessed,the source of study funding andany conflicts of interest statedby the investigators.”

MECIR conduct standard 44:Collect characteristics of theincluded studies in sufficientdetail to populate a table of‘Characteristics of includedstudies’.




PR26 Missing data Highly desirable Comment on how missing data

will be addressed.Briefly describe any plannedstrategies that will be used toaddress missing data. Thismight include imputation ofmissing outcome data forindividuals within studies (suchas worst-case or best-casescenarios), or imputations ofmissing standard deviations.Note that standard deviations

See Handbook SectionIII.3.3.3, Section 5.3.6 and Section 10.12.1

Cochrane Training resources: collecting data; analysingdichotomous outcomes; analysing continuousoutcomes; assessing RoBincluded studies

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can sometimes be computedfrom other reported statistics.

MECIR conduct standard 47:Collect and utilize the mostdetailed numerical data thatmight facilitate similar analysesof included studies. Where 2×2tables or means and standarddeviations are not available,this might include effectestimates (e.g. odds ratios,regression coefficients),confidence intervals, teststatistics (e.g. t, F, Z, Chi2) or Pvalues, or even data forindividual participants.

MECIR conduct standard 64:Consider the implications ofmissing outcome data fromindividual participants (due tolosses to follow-up orexclusions from analysis).

PR27 Tools to assess risk of bias inindividual studies

Mandatory

State and reference the tool(s)that will be used to assess riskof bias for included studies,how the tool(s) will beimplemented, and the criteriathat will be used to assign studyresults to judgements of lowrisk, high risk and unclear riskof bias

Different tools are likely to beappropriate for different typesof studies (e.g. randomizedtrials and non-randomizedstudies). If the current Handbook guidance forundertaking ‘Risk of bias’assessments will be followed inits entirety, then a reference tothe Handbook is sufficient toprovide the criteria used toassign judgements. Justify anyintended deviations from thetool.

MECIR conduct standard20: Plan in advance themethods to be used forassessing risk of bias inincluded studies, including thetool(s) to be used, how thetool(s) will be implemented, andthe criteria used to assign studyresults to judgements of lowrisk, high risk and unclear riskof bias.

MECIR conduct standard 52:Assess the risk of bias in atleast one specific result foreach included study. Forrandomized trials, the RoB 2tool should be used, involvingjudgements and support forthose judgements across a

See Handbook SectionIII.3.3.3, Section 7.1.2 and Chapter 8.

Cochrane Training resources: assessing RoB includedstudies and Rob 2.0 webinar

CIL: module 5 - introduction tostudy quality and risk of bias

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series of domains of bias, asdescribed in Handbook (version 6).


PR28 ‘Risk of bias’ assessmentprocess

Mandatory

State how risk of bias will beassessed, clarifying how manypeople will be involved (andwhether they will workindependently), and howdisagreements will be resolved.

MECIR conduct standard53: Use (at least) two peopleworking independently to applythe ‘Risk of bias’ tool to eachincluded study, and define inadvance the process forresolving disagreements.

If the Risk of Bias 2 tool (see Handbook (version 6) Chapter8) is to be used, state whetherinterest will be in the effect ofassignment to intervention orthe effect of adhering tointervention, and explain howresults will be selected to beassessed for risk of bias (i.e. forwhich outcome domains,outcome measures, time pointsand analyses).

See Handbook SectionIII.3.3.3, Section 7.3.2 and Chapter 8

Cochrane Training resources: assessing RoB includedstudies and Rob 2.0 webinar


PR29 Measures of effect Mandatory State the effect measures that

will be used to describe effectsizes in any included studies ormeta-analyses, or both (e.g.risk ratio or odds ratio, meandifference or standardizedmean difference).

See Handbook Section III.3.3.3

Cochrane Training resources: analysing dichotomousoutcomes and analysingcontinuous outcomes


PR30 Unit of analysis issues Mandatory If designs other than

individually randomized,parallel-group randomizedtrials are likely to be included,describe any methods that willbe used to address clustering,matching or other designfeatures of the included studies

In some circumstances,specific study designs are likelyto be identified in which unit-of-analysis errors might arise. Thisincludes cluster-randomizedtrials, cross-over trials, trialsinvolving multiple body partsand non-randomized studieswith clustered designs.

MECIR conduct standard 70:Consider the impact on theanalysis of clustering, matchingor other non-standard designfeatures of the included studies.


Cochrane Training resource: non-standard data and studydesigns


PR31 Studies with more than twogroups

Highly desirable

If multi-arm studies are likely tobe included, explain how theywill be addressed and

Note that it is mandatory todescribe these methods in thefull version of the review if

See Handbook SectionIII.3.3.3, Section 6.2.9 and Chapter 11.

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incorporated into syntheses. studies with more than one armare identified and included.

MECIR conduct standard 66: Ifmulti-arm studies are included,analyse multiple interventiongroups in an appropriate waythat avoids arbitrary omission ofrelevant groups and double-counting of participants.

Cochrane Training resource: non-standard data and studydesigns


PR32 Quantitative synthesis Mandatory Describe any intended

statistical methods forcombining results acrossstudies (e.g. meta-analysis,subgroup analysis, meta-regression, sensitivity analysis),including methods forassessing heterogeneity (e.g.I2, Tau2, statistical test).

In the majority of reviews, mostof this information is locatedunder the subheading ‘Datasynthesis’. Note, however, thatadditional subheadings shouldbe used to provide details ofsubgroup analyses,assessment of heterogeneityand sensitivity analysis.

MECIR conduct standard 21:Plan in advance the methods tobe used to synthesize theresults of the included studies,including whether a quantitativesynthesis is planned, howheterogeneity will be assessed,choice of effect measure (e.g.odds ratio, risk ratio, riskdifference or other fordichotomous outcomes), andmethods for meta-analysis (e.g.inverse variance or MantelHaenszel, fixed-effect orrandom-effects model).

MECIR conduct standard 62:Undertake (or display) a meta-analysis only if participants,interventions, comparisons andoutcomes are judged to besufficiently similar to ensure ananswer that is clinicallymeaningful.

MECIR conduct standard63: Assess the presence andextent of between-studyvariation when undertaking ameta-analysis.

See Handbook SectionIII.3.3.3, Section 1.5 and Section 10.10.2.

Cochrane Training resources: introduction tometa-analysis and exploringheterogeneity


PR33 Non-quantitative synthesis Mandatory Describe any intended non-

statistical methods forsynthesizing findings acrossstudies (sometimes referred toas narrative or qualitativesynthesis).

It may be apparent that a meta-analysis is unlikely, in whichcase methods should beprespecified for how thefindings of the included studieswill be compared andcontrasted.

See Handbook Chapter 12

Cochrane Training resources: Cochrane Consumers &Communication Data Synthesisand Analysis

CIL: module 8 - reporting the

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reviewPR34 Risk of reporting bias across

studiesHighly desirable

Describe any methods that willbe used for assessing the riskof reporting biases such aspublication bias.


Cochrane Training resources: small study effects andreporting biases


PR35 Addressing risk of bias Mandatory Describe how studies with high

or variable risks of bias will beaddressed in the synthesis.

Several options are availablefor addressing risk of bias in asynthesis, including reportingseparate syntheses for studiesat different risks of bias,restricting analysis to studies atlow (or low and unclear) risk ofbias only, and undertakingsensitivity analysis to examinethe impact of risks of bias onthe conclusions. Anunderstanding of the impact ofrisks of bias is important toinform GRADE assessments.

MECIR conduct standard 58:Address risk of bias in thesynthesis (whether quantitativeor non-quantitative). Forexample, present analyses thatare stratified according tosummary risk of bias, restrictedto studies at low risk of bias orrestricted to low-and-some-concerns of risk of bias

See Handbook Section 7.6.1and Chapter 8

Cochrane Training resources: assessing RoB includedstudies and RoB 2.0 webinar

PR36 Subgroup analyses Mandatory If subgroup analysis (or meta-

regression) are planned, statethe potential effect modifierswith rationale for each.

MECIR conduct standard22: Predefine potential effectmodifiers (e.g. for subgroupanalyses) at the protocol stage,restrict these in number, andprovide rationale for each.




PR37 Methods for economicevidence

Mandatory

If health economics evidence isto be reviewed, state themethods to be used to assessand synthesize this evidence.



PR38 Methods for qualitative

research evidenceMandatory

If qualitative research evidenceis to be reviewed, state themethods to be used to assessand synthesize this evidence.


Cochrane Training resource: Webinar - GRADE CERQual

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PR39 Certainty of the evidence Mandatory State the methods to be used to

assess the certainty of the bodyof evidence (using the fiveGRADE considerations).

If the current GRADE guidancefor these assessments will befollowed in its entirety (see Handbook Chapter 14), then areference to this is sufficient toprovide the criteria used tomake judgements.

MECIR conduct standard 74:Use the five GRADEconsiderations (risk of bias,consistency of effect,imprecision, indirectness andpublication bias) to assess thecertainty of the body ofevidence for each outcome,and to draw conclusions aboutthe certainty of evidence withinthe text of the review.


Cochrane Training resource: GRADE approach to evaluatingevidence quality


PR40 'Summary of findings’ table Mandatory State which outcomes and

comparisons it is planned willbe included in a ‘Summary offindings’ table.

A maximum of seven importantoutcomes should beprespecified for inclusion in a‘Summary of findings’ table(see Handbook Chapter 14). Ifpossible, sources of anyassumed risks to be presentedin a ‘Summary of findings’ tableshould be explained.

MECIR conduct standard 23:Plan in advance the methods tobe used for assessing thecertainty of the body ofevidence, and summarizing thefindings of the review.

See Handbook Section III.3.3.3and Section 1.5

Cochrane Training resource: Summary of Findings tables.


CIL: module 8 - reporting thereview

Acknowledgements (PR41)

Acknowledgements

Standard Rationale and elaboration ResourcesPR41 Acknowledgements Mandatory Acknowledge the contribution

of people not listed as authorsof the protocol, including anyassistance from the CochraneReview Group, non-authorcontributions and the role of anyfunders.


Cochrane Training resource: writing a protocol

Contribution of authors (PR42)

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Contribution of authors

Standard Rationale and elaboration ResourcesPR42 Contributions of authors Mandatory Describe the contributions of

each author to the protocol. See Handbook Section III.3.7


Declarations of interest (PR43)

Declarations of interest

Standard Rationale and elaboration ResourcesPR43 Declarations of interests Mandatory Report relevant present or

recent (three years prior todeclaration) affiliations or otherinvolvement in any organizationor entity with an interest in thereview’s findings that mightlead to a real or perceivedconflict of interest

The detailed policy for declaringrelevant interests is available inthe Cochrane Editorial andPublishing Policy Resource(EPPR). In brief, the nature andextent of the affiliation orinvolvement (whether financialor non-financial) should bedescribed. Declarations ofinterest should be statedaccording to the relevantcriteria from the InternationalCommittee of Medical JournalEditors (ICMJE), and must beconsistent with interestsdeclared on the Disclosure ofPotential Conflicts of Interestform.



Sources of support (PR44)

Sources of support

Standard Rationale and elaboration ResourcesPR44 Sources of support Mandatory List sources of financial and

non-financial support for thereview and the role of thefunder, if any.



Citation

Citation for the Standards for reporting of new Cochrane Intervention Reviews

Please cite this section as: Lasserson T, Churchill R, Chandler J, Tovey D, Thomas J, Flemyng, E, Higgins JPT. Standards for thereporting of protocols of new Cochrane Intervention reviews. In: Higgins JPT, Lasserson T, Chandler J, Tovey D, Thomas J,Flemyng E, Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, February 2021.

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Standards for the REPORTING of new Cochrane Intervention Reviews (R1-R109) Key points and introductionKey points:

Authors should consult the MECIR reporting standards before and during writing up of their review.The reporting standards are compatible with key reporting guidelines developed by different bodies, includingPRISMA.Abstracts and Plain language summaries need to be consistent with each other, and with the main text of thereview. Clear and consistent reporting supports replication of systematic reviews and should make updating easier.

Authors should consult these reporting Standards before and during writing up of their review. Adherence to the Standards will helpauthors to prepare an informative, readable review. It will also help to make editorial evaluation of their work efficient. It is especiallyimportant to declare and justify differences to the planned question or eligibility criteria, since these may indicate important changesto the scope of the review. Where any search, data collection and analysis methods used are different from those planned, this alsoneeds to be reported and explained. The reporting Standards are available from within Review Manager (RevMan) softwareaccording to the heading or subheading to which they relate.

Several reporting guidelines are already available for primary studies and systematic reviews, and have been compiled by the Equator Network[1]. MECIR Standards are compatible with the core items in two key sources of reporting guidance for systematicreviews: the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), and the US Institute of Medicine’sstandards for systematic reviews.

Accurately summarizing the key findings of a Cochrane Review in its Abstract and Plain language summary serves an importantpurpose in knowledge translation. These standalone summaries help to convey the results of the review to a broad audience.Authors should take particular care to ensure that conclusions drawn in the main text of the review under ‘Implications for practice’and ‘Implications for research’ take account of the strength of evidence presented in the review, and are appropriately distilled inthe Abstract and Plain language summary.

Authors and editors should ensure that all parts of the review are succinct and readable, so that someone who is not an expert inthe area can understand it. The published review needs to signpost and structure information clearly to help orientate readers.Review methods should be reported in sufficient detail that others are in principle able to reproduce the findings. Clear reporting ofthe eligibility criteria and methods will also help future efforts to update and maintain the published version of the review.

Rachel ChurchillProfessor of Evidence Synthesis and Co-ordinating Editor Cochrane Common Mental Disorders GroupUniversity of York

[1] The Equator Network is a Library for health research reporting that provides a searchable database.

Reporting review conduct (R1-R55) Title and Authors (R1-R2)

Title and Authors

Standard Rationale and elaboration ResourcesR1 Format of title Highly desirable Follow the standard template

for a Cochrane Review title See Handbook Section II.1.3


R2 Authors Mandatory

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List names and affiliations of allauthors

See Handbook Section II.2


Abstract (R3-R18)

Abstract

Cochrane Training resource: common errors - summary versions of a review

Cochrane Interactive Learning: module 8 - reporting the review

Standard Rationale and elaboration ResourcesR3 Writing the Abstract Mandatory Prepare a structured Abstract

to provide a succinct summaryof the review. In the interests ofbrevity it is highly desirable forauthors to provide an Abstractof less than 700 words, and itshould be no more than 1000words in length.

Abstracts are a prominent,publicly accessible summary ofthe review that need to standalone. They should convey keyinformation about the reviewquestion and its findings, andbe informative to readers.

R4 Abstract, Background Mandatory Summarize the rationale and

context of the review. See Handbook Section III.3.1

R5 Abstract, Objectives Mandatory State the main objective(s),

preferably in a single concisesentence.

The objective(s) should beexpressed in terms that relateto the population(s),intervention comparison(s) and,where appropriate, outcomes ofinterest.


R6 Abstract, Search Methods Mandatory Provide the date of the last

search from which recordswere evaluated and that anystudies identified wereincorporated into the review,and an indication of thedatabases and other sourcessearched.

Abstracts should aim to givereaders brief, but key,information about thecomprehensiveness of thesearch and the currency of theinformation summarized by thereview.

The Abstract must include themonth and year of the set ofsearches up to which theconclusions of the review arevalid. This date should reflectthe date of the most recent setof searches from which allrecords have been screened forrelevance and any studiesmeeting the eligibility criteriahave been fully incorporatedinto the review (studies may beawaiting classification if, forexample, the review authors areawaiting translation or


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clarification from authors orsponsors).

Abstracts do not need to reporton recent repeat or ‘catch-up’searches whose results havenot been fully incorporated intothe review. However, discretionshould be applied if suchsearches identify a large bodyof evidence, the absence ofwhich may affect the reliabilityof the conclusions.

The amount of informationregarding the search should beindicative of the process ratherthan provide specific details. Inthe interests of brevity certaindetails regarding the overallprocess may need to be movedto the full text of the review.

Example: “CENTRAL,MEDLINE, Embase, five otherdatabases and three trialsregisters were searched on[date] together with referencechecking, citation searchingand contact with study authorsto identify additional studies”.

R7 Abstract, Selection criteria Mandatory Summarize eligibility criteria of

the review, includinginformation on study design,population and comparison.

Any extensions to eligibilitycriteria to address adverseeffects, economic issues orqualitative research should bementioned.


R8 Abstract, Data collection andanalysis

Mandatory

Summarize any noteworthymethods for selecting studies,collecting data, evaluating riskof bias and synthesizingfindings. For many reviews itmay be sufficient to state “Weused standard methodologicalprocedures expected byCochrane.”

This section of the Abstractshould indicate the rigour of themethods that underpin theresults reported subsequently inthe Abstract. It does not need toreplicate the detaileddescription of the methodsgiven in the main text of thereview.

Details of how many peoplewere involved in the screeningprocess and collection ofinformation about any includedstudies are not necessary in theAbstract. Key statisticalmethods may be given if notclear from the results thatfollow.

The Abstract should prioritize


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the disclosure of non-standardapproaches. For example,rather than disclosing alldomains applied in theassessment of bias, notablevariations on the standardapproach should be given, suchas use of non-standard tools.

R9 Abstract, Main results: numberof studies and participants

Mandatory

Report the number of includedstudies and participants.

The total number of includedstudies should be stated. Itmight be appropriate to providenumbers of studies andparticipants for specificcomparisons and mainoutcomes if the amount ofevidence differs substantiallyfrom the total. Numbers ofparticipants analysed shouldgenerally be presented inpreference to numbers recruited (e.g. randomized); it isimportant to be clear whichnumbers are being reported.For some types of data theremay be preferable alternativesto the number of participants(e.g. person-years of follow-up,number of limbs).


R10 Abstract, Main results: studycharacteristics

Highly desirable

Provide a brief description ofkey characteristics that willdetermine the applicability ofthe body of evidence (e.g. age,severity of condition, setting,study duration).

Summarizing the studycharacteristics will providereaders of the Abstract withimportant information about theapplicability of the includedstudies. This is particularlyimportant if the included studiesreflect a subgroup of thoseeligible for inclusion in thereview, for example, if thereview intended to address theeffects of interventions acrossall age groups, but includedstudies that only recruitedadolescents.


R11 Abstract, Main results: biasassessment

Mandatory

Provide a comment on thefindings of the biasassessment.

The ‘Risk of bias’ assessmentsare a key finding and form afundamental part of the strengthof the conclusions drawn in thereview. If risks of bias differsubstantially for differentcomparisons and outcomes,this should be mentioned.


R12 Abstract, Main results: findings Mandatory

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Report findings for all importantoutcomes, irrespective of thestrength and direction of theresult, and of the availability ofdata.

Findings should typicallyinclude concise informationabout the size of effect andcertainty of evidence for theoutcome (such as risk of bias,consistency of effect,imprecision, indirectness andpublication bias), for exampleusing GRADE.

Outcomes reported in theAbstract should not be selectedsolely on the basis of thefindings. In general, the sameoutcomes in the Abstractshould be presented in thePlain language summary and‘Summary of findings’ tables. Ifno studies measured theoutcome, then a commentshould be made to that effect.



R13 Abstract, Main results: adverseeffects

Mandatory

Ensure that any findings relatedto adverse effects are reported.If adverse effects data weresought, but availability of datawas limited, this should bereported.

The Abstract of the reviewshould aim to reflect a balancedsummary of the benefits andharms of the intervention.


R14 Abstract, Main results: formatof numerical results

Mandatory

Present summaries of statisticalanalyses in the same way asthey are reported in the reviewand in a standard way, ensuringthat readers will understand thedirection of benefit and themeasurement scale used, andthat confidence intervals areincluded where appropriate.

The standard format forreporting the results ofstatistical analysis includes anindication of the summarymeasure, point estimate andconfidence interval, e.g. oddsratio 0.75 (95% confidenceinterval 0.62 to 0.89).

R15 Abstract, Main results:interpretability of findings

Highly desirable

Ensure that key findings areinterpretable, or are re-expressed in an interpretableway. For instance, they mightbe re-expressed in absoluteterms (e.g. assumed andcorresponding risks, NNTBs,group means), and outcomescombined with a standardizedscale (e.g. standardized meandifference) might be re-expressed in units that aremore naturally understood.

Absolute effects provide auseful illustration of the likelyimpact of intervention, and areusually easier to understandthan relative effects. Unitsexpressed on a standardizedscale reflect the effect estimateas the number of standarddeviations. This is not intuitiveto many readers who may bemore familiar with specificscales. Any re-expressedfindings must have beenpresented in the same way inthe main text of the review (seeprevious standard).

R16 Abstract, Authors’ conclusions Mandatory

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State key conclusions drawn. Authors’ conclusions mayinclude both implications forpractice and implications forresearch. Care must be takento avoid interpreting lack ofevidence of effect as evidenceof lack of effect.

Recommendations for practiceshould be avoided.

See Handbook Section III.3.1and Section 15.6.1

R17 Completeness of main reviewtext

Mandatory

Ensure that all findings reportedin the Abstract and Plainlanguage summary, including re-expressions of meta-analysisresults, also appear in the maintext of the review.

See Handbook SectionIII.3.1 and Section III.4

Cochrane Trainingresource: Common errors -inconsistency & inaccuracy

R18 Consistency of summary

versions of the reviewMandatory

Ensure that reporting ofobjectives, important outcomes,results, caveats andconclusions is consistentacross the main text, theAbstract, the Plain languagesummary and the ‘Summary offindings’ table (if included).

Summary versions of thereview should be written on theassumption that they are likelyto be read in isolation from therest of the review.

Cochrane Training resource: Common errors - inconsistency& inaccuracy

Background (R19-R25)

Background



Standard Rationale and elaboration ResourcesR19 Background Mandatory Provide a concise description of

the condition or problemaddressed by the reviewquestion, definition of theintervention and how it mightwork, and why it is important todo the review.

Systematic reviews shouldhave a clearly defined and well-reasoned rationale that hasbeen developed in the contextof existing knowledge. Outliningthe context of the reviewquestion is useful to readersand helps to establish keyuncertainties that the reviewintends to address

R20 Background headings Highly desirable Include the four standard

RevMan headings when writingthe Background.

Four standard headings areincluded in RevMan(‘Description of the condition’,


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‘Description of the intervention’,‘How the intervention mightwork’, and ‘Why it is importantto do this review’).

R21 Background references Mandatory Back up all key supporting

statements with references.Claims or statements regardingaspects such as diseaseburden, morbidity, prevalenceand mechanisms of actionshould be substantiated and,where available, supported byexternal evidence.

R22 Main objective Mandatory State the main objective, where

appropriate in a single concisesentence.

The primary objective of aCochrane Review should be toassess the effects of one ormore healthcare interventionson user-important outcomes,both intended and unintended.The objective should beexpressed in terms that relateto the population(s),intervention comparison(s) and,where appropriate, to specifythe outcomes of interestexplicitly. Review users may bepatients, carers, policy makers,clinicians, practitioners orothers.

MECIR conduct standard 2:Define in advance theobjectives of the review,including participants,interventions, comparators andoutcomes (PICO).

Where possible, the formatshould be of the form “Toassess the effects of [intervention orcomparison] for [healthproblem] for/in [types ofpeople, disease or problemand setting if specified]”.

See Handbook SectionIII.3.2 and Section 2.3

R23 Secondary objectives Highly desirable State explicitly (as secondary

objectives) any specificquestions being addressed bythe review, such as thoserelating to particular participantgroups, interventioncomparisons or outcomes.

The objectives should beexpressed in terms that relateto the population(s),intervention comparison(s) and,where appropriate, outcomes ofinterest.

MECIR conduct standard 4:Consider in advance whetherissues of equity and relevanceof evidence to specificpopulations are important to thereview, and plan for appropriatemethods to address them if

See Handbook SectionIII.3.2 and Section 2.4

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they are. Attention should bepaid to the relevance of thereview question to populationssuch as low-socioeconomicgroups, low- or middle-incomeregions, women, children andolder people.

R24 Economic evidence Mandatory If health economics evidence is

being reviewed, state thisexplicitly in the Objectives (as asecondary objective).

The primary aim of a CochraneReview should be to assess theeffects of one or morehealthcare interventions on user-important outcomes, bothintended and unintended.These outcomes may includeeconomic outcomes. If healtheconomics evidence is beingreviewed as an integratedeconomics component, thisshould be stated as asecondary objective.


CIL: module 9 - introduction tohealth economics

R25 Qualitative research evidence Mandatory If qualitative research evidence

is being reviewed, state thisexplicitly in the Objectives (as asecondary objective).

The primary aim of a CochraneReview should be to assess theeffects of one or morehealthcare interventions on user-important outcomes, bothintended and unintended. Ifqualitative research evidence isbeing included to ‘extend’ thereview, this should be stated asa secondary objective.


Methods (R26)

Methods

Standard Rationale and elaboration ResourcesR26 Reference protocol Highly desirable Cite the protocol for the review. The reader should be made

aware that the review is basedon a published protocol. This isparticularly important if thereview has been split intomultiple reviews since theprotocol was published. Themost convenient place toreference the protocol for thereview is under ‘Otherpublished versions of thisreview’. Since the protocol isusually no longer included in theCDSR once the review ispublished, it should be citedusing the last publicationcitation for the protocol.

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Archived versions of protocolscan be accessed via the currentversion of the review.

Criteria for considering studies for this review (R27-R32)

Criteria for considering studies for this review



Standard Rationale and elaboration ResourcesR27 Eligibility criteria for types of

study: study designsMandatory

State eligible study designs,and provide a justification forthe choice.

It is not necessary to explainwhy randomized trials areeligible (if that is the case),although it may be important toexplain why other types of studymeet the eligibility criteria of thereview.

MECIR conduct standard 9:Define in advance the eligibilitycriteria for study designs in aclear and unambiguous way,with a focus on features of astudy's design rather thandesign labels.

MECIR conduct standard 11:Justify the choice of eligiblestudy designs.


R28 Eligibility criteria for types ofstudy: study reports

Mandatory

If studies are excluded on thebasis of publication status orlanguage of publication, explainand justify this.

Studies should be includedirrespective of their publicationstatus and language ofpublication, unless explicitlyjustified.

MECIR conduct standard 12:Include studies irrespective oftheir publication status, unlessexclusion is explicitly justified.


R29 Eligibility criteria for types ofparticipants

Mandatory

State eligibility criteria forparticipants, including anycriteria around location, setting,diagnosis or definition ofcondition and demographicfactors, and how studiesincluding subsets of relevantparticipants are addressed.

Any notable restrictions on theeligibility criteria of the reviewshould be given and explained(e.g. exclusion of people underor over a certain age, specificsettings of intervention).

MECIR conduct standard 5:


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Define in advance the eligibilitycriteria for participants in thestudies.

MECIR conduct standard 6:Define in advance how studiesthat include only a subset ofrelevant participants will beaddressed.

R30 Eligibility criteria for types ofinterventions

Mandatory

State eligibility criteria forinterventions and comparators,including any criteria arounddelivery, dose, duration,intensity, co-interventions andcharacteristics of complexinterventions.

MECIR conduct standard7: Define in advance the eligibleinterventions and theinterventions against whichthese can be compared in theincluded studies.


R31 Role of outcomes Mandatory If measurement of particular

outcomes is used as aneligibility criterion, state andjustify this.

Studies should never beexcluded from a review solelybecause no outcomes ofinterest are reported. However,on occasion it will beappropriate to include onlystudies that measuredparticular outcomes. Forexample, a review of a multi-component public healthintervention promoting healthylifestyle choices, focussing onreduction in smokingprevalence, might legitimatelyexclude studies that do notmeasure smoking rates.

MECIR conduct standard 8:Clarify in advance whetheroutcomes listed under 'Criteriafor considering studies for thisreview' are used as criteria forincluding studies (rather thanas a list of the outcomes ofinterest within whicheverstudies are included).

See Handbook Section SectionIII.3.3.1 and Section 3.2.4.1

R32 Outcomes of interest Mandatory Define in advance outcomes

that are critical to the review,and any additional importantoutcomes, and defineacceptable ways of measuringthem.

Explain how multiple variants ofoutcome measures (e.g.definitions, assessors, scales,time points) are addressed.

MECIR conduct standard14: Define in advanceoutcomes that are critical to thereview, and any additionalimportant outcomes


See Handbook Section Section III.3.3.1 and Section3.2.4.1

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Search methods for identification of studies (R33-R38)

Search methods for identification of studies


Cochrane Interactive Learning: module 3 - searching for studies

Standard Rationale and elaboration ResourcesR33 Search sources Mandatory List all sources searched,

including: databases, trialsregisters, websites and greyliterature. Database namesshould include platform orprovider name (or both), anddates of coverage; websitesshould include full name andURL. State whether referencelists were searched andwhether individuals ororganizations were contacted.



See Handbook SectionIII.3.3.2, Section 1.5, Section4.3.1.1 and Section 4.4.5

R34 Latest searches Mandatory Provide the date of the last

search and the issue or versionnumber (where relevant) foreach database for which resultswere evaluated andincorporated into the review. Ifa search was rerun prior topublication, and its results werenot incorporated, explain howthe results were dealt with, andprovide the date of the search.

The review should provide thesearch date up to which studieshave been retrieved andassessed for inclusion. This isthe date to which theconclusions of the review arevalid. It should reflect the dateof the most recent set ofsearches from which all recordshave been screened forrelevance and any studiesmeeting the eligibility criteriahave been fully incorporatedinto the review (studies may beawaiting classification if, forexample, the review authors areawaiting translation orclarification from authors orsponsors).

Since the review is likely tohave drawn on searchesconducted across multipledatabases, it is possible thatsearches were performed onmore than one date. Theearliest date of the most recentset of searches should beprovided in the review text andas the hard-coded date of thelast search. The remainingdates for other databases


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should be reported in anAppendix.

If a ‘catch-up’ search was runsubsequent to the review beingwritten up, any relevant studiesnot yet assessed for inclusionshould be listed in the section‘Studies awaiting assessment’.

MECIR conduct standard37: Rerun or update searchesfor all relevant databases within12 months before publication ofthe review or review update,and screen the results forpotentially eligible studies.

MECIR conduct standard 38:Incorporate fully any studiesidentified in the rerun or updateof the search within 12 monthsbefore publication of the reviewor review update.

R35 Search restrictions Mandatory Specify and justify any

restrictions placed on the timeperiod covered by the search.

MECIR conduct standard 35:Justify the use of anyrestrictions in the searchstrategy on publication date orpublication format.

See Handbook SectionIII.3.3.2, and Section 4.4.5

R36 Searches for different types ofevidence

Mandatory

If the review has specificeligibility criteria concerninginclusion of additional studiessuch as studies of adverseeffects, health economicsevidence or qualitativeresearch evidence, describesearch methods for identifyingsuch studies.

Some reviews extend beyond afocus on the effects ofhealthcare interventions andaddress specific additionaltypes of evidence. These arediscussed in the Handbook.

MECIR conduct standard 26: Ifthe review has specificeligibility criteria around studydesign to address adverseeffects, economic issues orqualitative research questions,undertake searches to addressthem.

These are discussed in the Handbook Chapters 19, 20 and21.

R37 Search strategies forbibliographic databases

Mandatory

Present the exact searchstrategy (or strategies) used foreach database in an Appendix,including any limits and filtersused, so that it could bereplicated.

Search strategies that areavailable elsewhere (e.g.standard methodological filters,or strategies used to populate aspecialized register) may bereferenced rather thanreproduced. Including thenumber of hits for each line inthe strategy is optional.

MECIR conduct standard 36:


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Document the search processin enough detail to ensure that itcan be reported correctly in thereview.

Also MECIR conduct standards32–35.

R38 Search strategies for othersources

Highly desirable

Report the search terms usedto search any sources otherthan bibliographic databases(e.g. trials registers, the web),and the dates of the searches.

Some of this information mightbe better placed in anAppendix.



Data collection and analysis (R39-R55)

Data collection and analysis

Standard Rationale and elaboration ResourcesR39 Inclusion decisions Mandatory State how inclusion decisions

were made (i.e. from searchresults to included studies),clarifying how many peoplewere involved and whether theyworked independently.

MECIR conduct standard39: Use (at least) two peopleworking independently todetermine whether each studymeets the eligibility criteria, anddefine in advance the processfor resolving disagreements.


Cochrane Trainingresource: selecting studies


R40 Data collection process Mandatory State how data were extracted

from reports of includedstudies, clarifying how manypeople were involved, whetherthey worked independently, andhow disagreements wereresolved. Describe datacollection process for anyreports requiring translation.

MECIR conduct standard 43:Use a data collection form thathas been piloted.

MECIR conduct standard 45:Use (at least) two peopleworking independently toextract study characteristicsfrom reports of each study, anddefine in advance the processfor resolving disagreements.


Cochrane Trainingresource: collecting data


R41 Requests for data Highly desirable Describe attempts to obtain or

clarify data from individuals ororganizations.

MECIR conduct standard49: Seek key unpublishedinformation that is missing fromreports of included studies.




R42 Data items Mandatory

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State the types of informationthat were sought from reports ofincluded studies.

MECIR conduct standard44: Collect characteristics ofthe included studies in sufficientdetail to populate a table of‘Characteristics of includedstudies’.




R43 Transformations of data Mandatory Explain any transformations of

reported data prior topresentation in the review,along with any assumptionsmade. Explain any proceduresfor extracting numeric data fromgraphs.

MECIR conduct standard47: Collect and utilize the mostdetailed numerical data thatmight facilitate similar analysesof included studies. Where 2×2tables or means and standarddeviations are not available,this might include effectestimates (e.g. odds ratios,regression coefficients),confidence intervals, teststatistics (e.g. t, F, Z, Chi2) or Pvalues, or even data forindividual participants.




R44 Missing outcome data Highly desirable Explain how missing outcome

data were addressed.Describe how assumptions areapplied for missing data, e.g.last observation carriedforward, or assumptions ofparticular values such as worst-case or best-case scenarios.




R45 Tools to assess risk of bias inindividual studies

Mandatory

State and reference the tool(s)used to assess risk of bias forincluded studies, how thetool(s) was implemented, andthe criteria used to assignstudies to judgements of lowrisk, high risk and unclear riskof bias.

If the Handbook guidance forundertaking ‘Risk of bias’assessments was followed in itsentirety, then a reference to the Handbook is sufficient toprovide the criteria used toassign judgements. Justify anydeviations from the tool.

MECIR conduct standard 52:Assess the risk of bias in atleast one specific result foreach included study. Forrandomized trials, the RoB 2tool should be used, involvingjudgements and support forthose judgements across aseries of domains of bias, asdescribed in the Handbook.

MECIR conduct standards53 – 61


Cochrane Trainingresources: assessing RoBincluded studies and RoB 2.0webinar


R46 Effect measures Mandatory State the effect measures used See Handbook Section III.3.3.3

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by the review authors todescribe effect sizes (e.g. riskratio, mean difference) in anyincluded studies or meta-analyses, or both.

Cochrane Trainingresources: analysingdichotomous outcomes and analysing continuous outcomes


R47 Non-standard designs Mandatory If designs other than

individually randomized,parallel-group randomizedtrials are included, describeany methods used to addressclustering, matching or otherdesign features of the includedstudies.

MECIR conduct standard 70:Consider the impact on theanalysis of clustering, matchingor other non-standard designfeatures of the included studies.




R48 Studies with more than twogroups

Mandatory

If multi-arm studies areincluded, explain how they wereaddressed and incorporatedinto syntheses.

MECIR conduct standard 66: Ifmulti-arm studies are included,analyse multiple interventiongroups in an appropriate waythat avoids arbitrary omission ofrelevant groups and double-counting of participants.




R49 Assessing heterogeneity Mandatory Describe the methods used to

identify the presence ofheterogeneity between thestudies in the review (e.g. non-quantitative assessment, I2,Tau2 or statistical test).

MECIR conduct standard 69:Take into account anystatistical heterogeneity wheninterpreting the results,particularly when there isvariation in the direction ofeffect.


MECIR conduct standard 63:Assess the presence andextent of between-studyvariation when undertaking ameta-analysis.

See Handbook Section 10.10.2and Section 10.10.3



R50 Risk of reporting bias acrossstudies

Highly desirable

Describe any methods used forassessing the risk of reportingbiases such as publication bias.


Cochrane Training resource: small study effects & reportingbiases

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R51 Data synthesis Mandatory Describe any methods used for

combining results acrossstudies. Where data have beencombined in statistical softwareexternal to RevMan, referencethe software, commands andsettings used to run theanalysis.

Decisions to depart fromintended methods, for examplean alternative statistical model,should be reported andjustified.


Cochrane Training resource: intro to meta-analysis


R52 Subgroup analyses Mandatory If subgroup analysis (or meta-

regression) was performed,state the potential effectmodifiers with rationale foreach, stating whether each wasdefined a priori or post hoc andhow they were compared (e.g.statistical tests).

MECIR conduct standard 22:Predefine potential effectmodifiers (e.g. for subgroupanalyses) at the protocol stage,restrict these in number, andprovide rationale for each.

MECIR conduct standard 67: Ifsubgroup analyses are to becompared, and there arejudged to be sufficient studiesto do this meaningfully, use aformal statistical test tocompare them.

See Handbook SectionIII.3.3.3 and Section 10.11.3.1



R53 Addressing risk of bias Mandatory Describe how studies with high

or variable risks of bias areaddressed in the synthesis.

MECIR conduct standard 58:Address risk of bias in thesynthesis (whether quantitativeor non-quantitative). Forexample, present analyses thatare stratified according tosummary risk of bias, restrictedto studies at low risk of bias orrestricted to low-and-some-concerns of risk of bias.


Cochrane Trainingresources: assessing RoBincluded studies and RoB 2.0webinar


R54 Sensitivity analysis Mandatory State the basis for any

sensitivity analyses performed.MECIR conduct standard71: Use sensitivity analyses toassess the robustness ofresults, such as the impact ofnotable assumptions, imputeddata, borderline decisions andstudies at high risk of bias.


Cochrane Trainingresources: assessing RoBincluded studies and exploringheterogeneity


R55 Summary of findings Highly desirable State any methods for

summarizing the findings of thereview, including theassessment of the certainty ofthe body of evidence for each

MECIR conduct standard75: Justify and document allassessments of the certainty ofthe body of evidence (forexample downgrading or


Common issues in Summary ofFindings tables.

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outcome. upgrading if using GRADE).





Results (R56-R109) Description of studies (R56-R72)

Description of studies

Standard Rationale and elaboration ResourcesR56 Flow of studies Mandatory Provide information on the flow

of studies from the number(s) ofreferences identified in thesearch to the number of studiesincluded in the review, ideallyusing a PRISMA type flowdiagram. Clarify how multiplereferences for the same studyrelate to the individual studies.

MECIR conduct standard 41:Document the selectionprocess in sufficient detail to beable to complete a flow diagramand a table of ‘Characteristicsof excluded studies’.

MECIR conduct standard 42:Collate multiple reports of thesame study, so that each study,rather than each report, is theunit of interest in the review.

See Handbook SectionIII.3.4.1, Section 4.6.4, Section4.6.2 and Section 5.2.1



R57 Lack of included studies Highly desirable If a review identifies no eligible

studies, restrict the Resultssection to a description of theflow of studies and any briefcomments about reasons forexclusion of studies.

Under ‘Risk of bias in includedstudies’ and ‘Effects ofinterventions’, state “No studymet the eligibility criteria”. Anydiscussion of evidence notmeeting the eligibility criteria ofthe review should be in theDiscussion section.


R58 Excluded studies Mandatory List key excluded studies and

provide justification for eachexclusion.

The table of ‘Characteristics ofexcluded studies’ is intended asan aid to users rather than acomprehensive list of studiesthat were identified but notincluded. List here any studiesthat a user might reasonablyexpect to find in the review toexplain why they are excluded.


Cochrane Training resource: selecting studies


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R59 Studies awaiting classification Highly desirable List the characteristics of any

completed studies that havebeen identified as potentiallyeligible but have not beenincorporated into the review.

Users of the review will beinterested to learn of anypotentially relevant studies thathave been conducted and areknown to the review team, buthave not yet been incorporatedin to the review irrespective oftheir publication status. This willhelp them to assess the stabilityof the review findings. Theseshould be listed in the table of‘Characteristics of studiesawaiting classification’, alongwith any details that are known.Authors should also considerthe impact of not includingthese studies on the reviewfindings as a potentiallimitation, and the extent towhich they affect theimplications for research.




R60 Ongoing studies Mandatory Provide details of any identified

studies that have not beencompleted.

Users of the review will beinterested to learn of anypotentially relevant studies thathave not been completed. Thiswill help them to assess thestability of the review findings.These should be listed in thetable of ‘Characteristics ofongoing studies’, along with anydetails that are known.

Cochrane Reviews should bemindful of research waste so itis useful to consider howongoing studies might addressthe review question under‘Implications for research’.




R61 Table of ‘Characteristics ofincluded studies’

Mandatory

Present a table of‘Characteristics of includedstudies’ using a uniform formatacross all studies.

MECIR conduct standard44: Collect characteristics ofthe included studies in sufficientdetail to populate a table of‘Characteristics of includedstudies’.




R62 Included studies Mandatory Provide a brief narrative

summary of any includedstudies. This should include thenumber of participants and asummary of the characteristicsof the study populations andsettings, interventions,comparators and funding



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sources.R63 Table of ‘Characteristics of

included studies’: methods Mandatory

Provide the basic study designor design features (e.g. parallelgroup randomized trial, cluster-randomized trial, controlledbefore and after study).

Even if the review is restrictedto one study design, thesetables should provide acomprehensive summary ofeach study. It is important thatlabels used to describe studydesigns are clearly defined inthe review.




R64 Table of ‘Characteristics of

included studies’: participantsMandatory

Provide sufficient informationabout the study populations toenable a user of the review toassess the applicability of thereview’s findings to their ownsetting.

Information presented in thistable should reflect the baselinedemographics of the studysample. In addition, it is helpfulto state the eligibility criteria ofthe study.




R65 Table of ‘Characteristics ofincluded studies’: sample sizes

Mandatory

Include the sample size foreach included study in the tableof ‘Characteristics of includedstudies’.

If sample sizes are available foreach intervention group, theseshould be included. Aconvenient place is often withinthe box for Interventions, e.g.inserting “(n = )” after eachlisted intervention group.




R66 Table of ‘Characteristics ofincluded studies’: interventions

Mandatory

Provide sufficient information toenable users of the review toassess the applicability of theintervention to their own setting,and if possible in a way thatallows the intervention to bereplicated.

The components of allinterventions (drug, non-drug,simple or complex) should bereported. Reporting guidelineshave been developed fordescribing interventions used inprimary research and reviewauthors may find it useful tostructure their description ofinterventions around the coreattributes highlighted by TIDieR(Hoffman 2014). Lengthyexplanations of interventionsshould be avoided. Citations tosources of detailed descriptionscan be included.




R67 Table of ‘Characteristics ofincluded studies’: outcomes

Mandatory

Provide clear and consistentinformation about outcomesmeasured (or reported), howthey were measured and thetimes at which they weremeasured.

It should be clear whether mainoutcomes of interest in thereview were measured in thestudy.



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R68 Table of ‘Characteristics ofincluded studies’: dates

Highly desirable

Include the dates when thestudy was conducted in thetable of ‘Characteristics ofincluded studies’.

If dates are not available thenthis should be stated (e.g.“Study dates not reported”).




R69 Table of ‘Characteristics ofincluded studies’: fundingsource

Mandatory

Include details of fundingsources for the study, whereavailable.

Details of funding sourcesshould be placed in this tablerather than as part of the ‘Riskof bias’ table. Including an extrarow in the table of‘Characteristics of includedstudies’ is encouraged.




R70 Table of ‘Characteristics ofincluded studies’: declarationsof interest

Mandatory

Include details of anydeclarations of interest amongthe primary researchers.

Declarations of interest shouldbe placed in this table ratherthan as part of the ‘Risk of bias’table. Including an extra row inthe table of ‘Characteristics ofincluded studies’ isencouraged.




R71 Choice of intervention groupsin multi-arm studies

Highly desirable

If a study is included with morethan two intervention arms,restrict comments on anyirrelevant arms to a briefcomment in the table of‘Characteristics of includedstudies’.

Intervention arms that are notrelevant to the review questionshould not be discussed indetail, although it is useful toclarify (in this table) that sucharms were present.

MECIR conduct standard 50: Ifa study is included with morethan two intervention arms,include in the review onlyintervention and control groupsthat meet the eligibility criteria.)


Cochrane Training resource: analysing non-standard dataand study designs


R72 References to included studies Mandatory List all reports of each included

study under the relevant StudyID.

It is important that all reportsare listed, and are grouped bystudy. Marking one report asthe primary reference is helpfulwhere appropriate.

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Risk of bias in included studies (R73-R75)

Risk of bias in included studies

Cochrane Training resource: assessing RoB included studies and RoB 2.0 webinar

Cochrane Interactive Learning: module 5 - introduction to study quality and risk of bias

Standard Rationale and elaboration ResourcesR73 'Risk of bias' table Mandatory Present at least one ‘Risk of

bias’ table for each study that isincluded in a synthesis, withjudgements about risks of bias,and explicit support for thesejudgements.

‘Risk of bias’ presentation toolsin RevMan should be usedwherever possible.

MECIR conduct standard52: Assess the risk of bias in atleast one specific result foreach included study. Forrandomized trials, the RoB 2tool should be used, involvingjudgements and support forthose judgements across aseries of domains of bias, asdescribed in the Handbook.

Also MECIR conduct standards54 – 61


R74 Summary assessments of riskof bias

Highly desirable

Present an overall risk of biasassessment across domains foreach key outcome for eachincluded study, and ensure thatthese are supported by theinformation presented in the‘Risk of bias’ tables.

MECIR conduct standard 57:Summarize the risk of bias foreach key outcome for eachstudy.

See Handbook Section 7.5 andChapter 8

R75 Risk of bias in included studies Mandatory Provide a brief narrative

summary of the risks of biasamong the included studies.

It may be helpful to identify anystudies considered to be at lowrisk of bias for particular keyoutcomes.

Effects of interventions (R76-R99)

Effects of interventions


Standard Rationale and elaboration ResourcesR76 Use of ‘Data and analysis’

headingsMandatory

Ensure appropriate use of anyheading hierarchy of

Appropriate use of thehierarchy in RevMan5 ensures

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Comparisons, Outcomes,Subgroups and Study data inthe ‘Data and analysis’ section.

consistency of structure acrossreviews. It is confusing for theuser if outcomes are listedagainst the heading‘Comparison’ and interventionslisted against the heading‘Outcome or subgroup’. Thisstandard will not be requiredwhen using the study-centricdata structure of RevMan Web.

R77 Presenting data Highly desirable Ensure that simple summary

data for each interventiongroup, as well as estimates ofeffect size (comparing theintervention groups), areavailable for each study foreach outcome of interest to thereview. These appear bydefault when dichotomous orcontinuous outcome data areanalysed within RevMan.

Simple summaries such asnumbers of events, means andstandard deviations should bepresented for each treatmentgroup when available. This isachieved primarily by using the‘Data and analyses’ section ofthe review, for dichotomous andcontinuous outcomes. For otheroutcomes, these shouldtypically be presented in tableslabelled ‘Other data’. Whendata for each separateintervention group are availablefor outcomes analysed as‘generic inverse-variance’ data,these might be presented inAdditional tables.

See Handbook SectionIII.3.4.4.

R78 Number of studies andparticipants

Mandatory

State how many studies andhow many participantscontributed data to results foreach outcome, along with theproportion of the includedstudies and recruitedparticipants potentiallyavailable for the relevantcomparison.

It is unlikely that the samenumber of studies willcontribute data to everyoutcome of interest. Specificstudies may contribute differentnumbers of participants fordifferent outcomes. Therefore,for each comparison, it ishelpful to indicate to readerswhat proportion of the relevantincluded studies and recruitedparticipants contribute data toeach outcome. Failure todisclose this may bemisleading.

R79 Source of data Highly desirable State the source of all data

presented in the review, inparticular, whether it wasobtained from publishedliterature, by correspondence,from a trials register, from aweb-based data repository, etc.

Transparency of data sourceenables validation orverification of data by others,including editors or readers ofthe review.

R80 Multiple outcome data Mandatory Describe any post hoc

decisions that might give rise toaccusations of selectiveoutcome reporting, for example

Transparent disclosure of posthoc decisions will enablereaders of the review to assessthe credibility of the results of

See Handbook Section 3.2.4.1and Section 5.4.1

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when there were multipleoutcome measures (e.g.different scales), multiple timepoints or multiple ways ofpresenting results.

the review for themselves. Posthoc decisions to change thedefinition or priority of outcomemeasures must be reported andjustified under ‘Differencesbetween the protocol andreview’.

MECIR conduct standard16: Define in advance details ofwhat are acceptable outcomemeasures (e.g. diagnosticcriteria, scales, compositeoutcomes).

MECIR conduct standard 17:Define in advance how outcomemeasures will be selected whenthere are several possiblemeasures (e.g. multipledefinitions, assessors orscales).

MECIR conduct standard 18:Define in advance the timing ofoutcome measurement.

R81 Ordering of results and ‘Dataand analysis’ section

Highly desirable

Organize results to follow theorder of comparisons andoutcomes specified in theprotocol, following in particularthe distinction between primaryand secondary outcomes.

Review authors must avoidselective reporting of analysisresults in a way that dependson the findings. The best way toachieve this is to follow a well-structured protocol and presentresults as outlined in thatprotocol. However, sometimesa pragmatic decision needs tobe made that an alternativearrangement is preferable,particularly with regard tocomparisons. This choiceshould be explicitly justified.

R82 Prespecified outcomes Mandatory Report synthesis results for all

prespecified outcomes,irrespective of the strength ordirection of the result. Indicatewhen data were not availablefor outcomes of interest, andwhether adverse effects datawere identified.

To avoid selective outcomereporting (in truth or inperception), the review shouldaddress all outcomes specifiedin the protocol.

R83 Statistical uncertainty Mandatory Accompany all effect size

estimates with a measure ofstatistical uncertainty (e.g. aconfidence interval with aspecified level of confidencesuch as 90%, 95% or 99%).

Confidence intervals are thepreferred method forexpressing statisticaluncertainty.


R84 P values Highly desirable

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If reporting P values, provideexact P values (e.g. P = 0.08rather than P > 0.05).

Effect estimates withconfidence intervals are thepreferred method of presentingnumeric results. P valuesshould not be used as analternative to confidenceintervals and should not beused to divide results into‘significant’ or ‘non-significant’;exact P values portray thestrength of evidence against thenull hypothesis.


R85 Tables and Figures Mandatory Link to each Table and Figure. All tables and figures should

have a brief descriptive captionand must be referred to innumerical order in the reviewtext.

R86 Number of Tables and Figures Highly desirable Keep the number of Tables and

Figures low to convey keyfindings without affecting thereadability of the review text.

Tables (typically implementedas Additional tables) andFigures (including RevMan flowcharts, RevMan forest plots andimported graphics) may beadded to reviews and includedin the body of the text. Reviewsshould try and avoid includingmore than six such Tables andFigures in total. Further Tablesand Figures can be included assupplementary material (e.g. as‘Data and analysis’ forest plotsor within Appendices).

R87 Consistency of results Mandatory Ensure that all statistical results

presented in the main reviewtext are consistent between thetext and the ‘Data and analysis’tables.

Errors can be introduced,particularly when analyses arererun.

R88 Direction of effect Mandatory State whether findings indicate

a clear direction of benefit.Where results indicate that anintervention is better or worsethan another intervention, it isimportant to make it clear whichintervention is favoured. This isthe case particularly whendifferent scales are combinedusing standardized meandifferences.


R89 Interpretability of results Mandatory Ensure that key findings are

interpretable, or are re-expressed in an interpretableway. For instance, they mightbe re-expressed in absoluteterms (e.g. assumed andcorresponding risks, NNTBs,group means), and outcomescombined with a standardized

Absolute effects provide auseful illustration of the likelyimpact of an intervention, andare usually easier to understandthan relative effects. They mayneed to be accompanied,however, with information aboutassumed baseline risks.Confidence intervals should be

Cochrane Training resources: analysing dichotomousoutcomes and analysingcontinuous outcomes

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scale (e.g. standardized meandifference) might be re-expressed in units that aremore naturally understood. Ifminimally important differenceswere prespecified or areavailable, these should beprovided to aid interpretation.

presented for NNTBs andsimilar summary measures. Re-expressing relative effects asabsolute effects often requiresthe specification of assumed(e.g. untreated) risks, and thesource of these should beprovided. Results expressed asstandardized mean differencesreflect the number of standarddeviations’ difference betweenmean responses. This is notintuitive to many readers whomay be more familiar withspecific scales. Ideally,minimally important effect sizesshould be specified in theprotocol.

R90 Studies without usable data Mandatory Comment on the potential

impact of studies thatapparently measuredoutcomes, but did notcontribute data that allowed thestudy to be included insyntheses.

There is good evidence ofselective outcome reportingamong clinical trials. Outcomesthat are believed to have beenmeasured but are not reportedin a usable format maytherefore be systematicallydifferent from those that areusable, and introduce bias.‘Usable’ in this sense refersboth to incorporation in a meta-analysis and to consideration innon-statistical syntheses offindings. Authors mightconsider using a table toindicate which studiescontributed data to theoutcomes of interest in thereview.

MECIR conduct standard40: Include studies in thereview irrespective of whethermeasured outcome data arereported in a ‘usable’ way.


R91 Missing outcome data Highly desirable Discuss the implications of

missing outcome data fromindividual participants (due tolosses to follow-up orexclusions from analysis).

MECIR conduct standard 64:Consider the implications ofmissing outcome data fromindividual participants (due tolosses to follow-up orexclusions from analysis).


R92 Skewed data Highly desirable Discuss the possibility and

implications of skewed datawhen analysing continuousoutcomes.

MECIR conduct standard65: Consider the possibility andimplications of skewed datawhen analysing continuousoutcomes.


Cochrane Trainingresource: analysing continuousoutcomes

Page 74/89


R93 Forest plots Highly desirable Present data from multiple

studies in forest plots (using the'Data and analyses' structure inRevMan) wherever possible,providing it is reasonable to doso.

Presenting data in forest plotscan be useful, even if thestudies are not combined in ameta-analysis.



R94 Multiple subgroup analysesand sensitivity analyses

Highly desirable

If presenting multiple sensitivityanalyses or different ways ofsubgrouping the same studies,present these in summary form(e.g. a single Table or Figure)and not in multiple forest plots.



R95 Labels on plots Mandatory Label the directions of effect

and the intervention groups inforest plots with theinterventions being compared.

By default, RevMan currentlyuses ‘experimental’ and‘control’ within labels. It ishelpful to replace these withmore specific interventionnames, and essential if theordering is swapped (or forhead-to-head comparisons).Directions of effect should beused as consistently aspossible within a review.



R96 Risk of bias across studies Highly desirable Present results of the

assessment of risk of biasacross studies (and acrossdomains) for each keyoutcome, and state whether thisleads to concerns about thevalidity of the review’s findings.

Considerations of risk of biasacross studies are required forassessments of the certainty ofthe body of evidence (e.g. usingGRADE).

Cochrane Training resources: assessing RoB includedstudies and RoB 2.0 webinar



R97 Reporting biases Highly desirable Present results of any

assessment of the potentialimpact of reporting biases onthe review’s findings.

MECIR conduct standard73: Consider the potentialimpact of reporting biases onthe results of the review or themeta-analyses it contains.


Cochrane Training resource: small study effects andreporting biases


R98 ‘Summary of findings’ table Mandatory Present a ‘Summary of findings’

table according torecommendations described inthe Handbook (version 5 orlater).

Specifically: include results forone clearly defined populationgroup (with few exceptions);indicate the intervention and thecomparison intervention;include seven or fewer patient-important outcomes; describe


Incorporating GRADE inCochrane Reviews

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the outcomes (e.g. scale,scores, follow-up); indicate thenumber of participants andstudies for each outcome;present at least one baselinerisk for each dichotomousoutcome (e.g. study populationor median/medium risk) andbaseline scores for continuousoutcomes (if appropriate);summarize the interventioneffect (if appropriate); andinclude a measure of thecertainty of the body ofevidence for each outcome.

Efforts should be made toincorporate informationpresented in ‘Summary offindings’ tables (such asabsolute effects, certaintyratings and downgradingdecisions) in other parts of thereview including the Abstract,Plain language summary,Effects of interventions,Discussion and Authors’conclusions.


R99 Assessments of the certainty ofthe body of evidence

Mandatory

Provide justification or rationalefor any measures of thecertainty of the body ofevidence for each key outcome.If a ‘Summary of findings’ tableis used, use footnotes toexplain any downgrading orupgrading according to theGRADE approach.


MECIR conduct standard 75:Justify and document allassessments of the certainty ofthe body of evidence (forexample downgrading orupgrading if using GRADE).



Incorporating GRADE inCochrane Reviews



Discussion (R100-R101)

Discussion


Standard Rationale and elaboration ResourcesR100 Discussion headings Highly desirable

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Include the standard RevManheadings when writing theDiscussion.

Five standard headings areincluded in RevMan (‘Summaryof main results’, ‘Overallcompleteness and applicabilityof evidence’, ‘Certainty of theevidence’, ‘Potential biases inthe review process,‘Agreements anddisagreements with otherstudies or reviews’).


R101 Limitations Mandatory Discuss limitations of the review

at study and outcome level (e.g.regarding risk of bias), and atreview level (e.g. incompleteidentification of studies,reporting bias).

Review authors must explicitlystate the limitations of theirreview. One aspect that iseasily overlooked is that ofadverse effects. In particular, ifthe review methods do notallow for detection of serious orrare adverse events, or both,the review authors mustexplicitly state this as alimitation. Additionalconsiderations here includecurrency and completeness ofthe search, completeness ofdata collection processes,assumptions made regardingclassification of interventions,outcomes or subgroups, andmethods used to account formissing data.

MECIR conduct standard73: Consider the potentialimpact of non-reporting biaseson the results of the review orthe meta-analyses it contains.


Authors' conclusions (R102-R103)

Authors' conclusions


Standard Rationale and elaboration ResourcesR102 Conclusions: implications for

practiceMandatory

Provide a general interpretationof the evidence so that it caninform healthcare or policydecisions. Avoid makingrecommendations for practice.

When formulating implicationsfor practice base conclusionsonly on findings from thesynthesis (quantitative ornarrative) of studies included inthe review. The conclusions ofthe review should convey theessence of the synthesis ofincluded studies, without

See Handbook Section III.3.6and Section 15.6.1


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selective reporting of theparticular findings on the basisof the result, and withoutdrawing on data that were notsystematically compiled andevaluated as part of the review.

R103 Conclusions: implications forresearch

Mandatory

If recommending furtherresearch, structure theimplications for research toaddress the nature of evidencerequired, including population,intervention comparison,outcome, and type of study.

Researchers and researchfunders are an important usergroup of Cochrane Reviews.Recommendations for futureresearch should offerconstructive guidance onaddressing the remaininguncertainties identified by thereview. This is particularlyimportant for reviews thatidentify few or no studies.Include any information aboutcompleted or ongoing studiesthat are likely to address thereview question.

Acknowledgements (R104)

Acknowledgements

Standard Rationale and elaboration ResourcesR104 Acknowledgements Mandatory Acknowledge the contribution

of people not listed as authorsof the review, including anyassistance from the CochraneReview Group, non-authorcontributions to searching, datacollection, study appraisal orstatistical analysis, and theprovision of funding.



Contribution of authors (R105)

Contribution of authors

Standard Rationale and elaboration ResourcesR105 Contributions of authors Mandatory Describe the contributions of

each author to the review. See Handbook Section III.3.7


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Declarations of interest (R106)

Declarations of interest

Standard Rationale and elaboration ResourcesR106 Declarations of interest Mandatory Report any current or recent

(within the 36 months prior toregistration of the review)financial interests relevant tothe topic of the review. Thismeans payments from anycommercial organization withan interest in the topic of thereview. Include the dates of theinvolvement.

Report any current or recent(within 36 months prior toregistration of the review) non-financial relationships andactivities that have a direct andobvious connection to the topicof the review. Include the datesof the involvement.

Report involvement in any studythat may be eligible for inclusionin the review.

Cochrane has two Conflict ofInterest policies relating toCochrane Library content.Which policy applies to aparticular review depends onwhether the review wasregistered before or after 14October 2020.

For reviews registered after 14October 2020 the CoI Policy forCochrane Library Content(2020) applies and for reviewsregistered before 14 October2020 the CommercialSponsorship Policy(2014) applies.

Declarations of interest shouldbe stated according to therelevant CoI policy and must beconsistent with interestsdeclared on the Disclosure ofPotential Conflicts of Interestform.

See Handbook Section III.3.7and EPPR Disclosure ofpotential conflict of interest byauthor policy


Differences between protocol and review (R107-R108)

Differences between protocol & review

Standard Rationale and elaboration ResourcesR107 Changes from the protocol Mandatory Explain and justify any changes

from the protocol (including anypost hoc decisions abouteligibility criteria or the additionof subgroup analyses).

MECIR conduct standard 13:Justify any changes to eligibilitycriteria or outcomes studied. Inparticular, post hoc decisionsabout inclusion or exclusion ofstudies should keep faith withthe objectives of the reviewrather than with arbitrary rules.


R108 Methods not implemented Mandatory Document aspects of the

protocol that were notimplemented (e.g. because nostudies, or few studies, werefound) in the section‘Differences between protocoland review’, rather than in theMethods section.

Including a record of methodsthat were not implementedhelps to retain specific detailsof the protocol. By doing so, thenext version of the review canbe seen to be coherent withwhat was planned in theprotocol.


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Sources of support (R109)

Sources of support

Standard Rationale and elaboration ResourcesR109 Sources of support Mandatory List sources of financial and

non-financial support for thereview and the role of thefunder, if any.



Reference

Reference

Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. (2014) Better reporting of interventions: template forintervention description and replication (TIDieR) checklist and guide. BMJ 2014;348:g1687. doi: 10.1136/bmj.g1687

Citation

Citation

Please cite this section as: Churchill R, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E, Higgins JPT. Standards for thereporting of new Cochrane Intervention Reviews. In: Higgins JPT, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E,Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, February 2021.

Standards for planning, conduct and reporting of UPDATES of CochraneIntervention Reviews (U1-U11, UR1-UR7) Key points and introductionKey points:

Before undertaking an update, authors should consider the currency and relevance of the question, as well asthe methodology used to address it.A new protocol will be required if important changes are made to the review question or the generalmethodology. An update should be conducted according to the standards required for any review, with the followingadditional requirements to ensure that any changes are managed appropriately and reported clearly to readers

Since its inception, Cochrane has advocated for the routine updating of systematic reviews, in order to take account of newevidence. However, before undertaking an update, it is important to consider carefully whether an update is warranted. SeeHandbook Chapter IV, section 2 for a framework and checklist on deciding whether or when to update a Cochrane Review. AllCRGs are encouraged to classify their reviews by their update status , to denote whether the review is up to date, an update ispending or no update is planned (see the Updating Classification System).

Several important decisions are required at the beginning of the planning of an update. The first is whether the original reviewquestion is still relevant. The second is whether the general methodological approach is still appropriate to answer the review

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question: this will need a review of the original protocol. Third, authors need to address whether the scope of the review isappropriate, whether it should be split into two or more reviews, or whether it should be merged with other reviews. Importantchanges of this nature indicate a need for a new protocol.

The following updating standards reflect three key stages: planning, conducting and reporting the update. Expectations are thatreview authors will consider each of these sections before updating a review. Authors should examine and address any feedbackon the original review before embarking on an update or a new derivative review. Planning an update should involve discussion withthe Cochrane Review Group (CRG) over the adoption of new methods or changes to the review question proposed. The followingstandards for updates should be used in conjunction with the conduct and reporting standards for new Cochrane Reviews andthese are cited where necessary.

Jackie ChandlerMethods Co-ordinator (2011-2018)Cochrane Editorial and Methods Department

Deciding on and performing an update (U1-U11, UR1-UR7) Planning the update (U1-U5)

Planning the update

Standard Rationale and elaboration ResourcesU1 Reconsidering review

questionsMandatory

Confirm or amend reviewquestion (PICO) andobjectives.

Consider whether it is importantto modify or add new objectivesto make the review relevant toits users.

Consider whether the reviewwill be split, merged withanother review or otherwisechanged substantially. If so, anew protocol might bewarranted and the MECIRconduct standards should befollowed rather than these update standards. It will benecessary to agree theapproach to updating thereview with the CRG.

MECIR conduct standards C1,C2

See Explanatory Note 1

See Handbook Section IV.3.1, Section 2.1 and Section 2.3

U2 Reconsidering outcomes Mandatory Confirm or amend outcomes of

interestConsider whether it isnecessary to modify or addoutcomes to ensure all user-important outcomes, includingadverse effects, are addressed.Define which outcomes areprimary outcomes and whichare secondary outcomes. Keepthe total number of outcomes

See Handbook Section 1.5, Section 2.1, Section 3.2.4.1, Section 5.4.1

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as small as possible. Considercore outcome sets whereavailable. Prioritize outcomesthat will be assessed with theGRADE considerations.

MECIR conduct standards C3, C14-C18, C23

U3 Reconsidering eligibility criteria Mandatory Confirm or amend eligibility

criteria.Changes to the reviewobjectives (e.g. additionalconsideration of rare adverseeffects, economic issues orqualitative issues) may requiremodification of the eligibilitycriteria, possibly extending thescope to additional types ofstudies.

U4 Planning the search Mandatory Decide appropriate search

methodsThere are four considerations inplanning search methods forupdates:

1. Changes to eligibilitycriteria may require thesearch methods to bemodified, or additionalsearch strategies to bedeveloped.

2. Additional sourcesmight need to besearched (e.g. trialsregisters) if notsearched for the lastpublished version of thereview. Considerationshould also be given tothe importance ofsearching datarepositories andinformation availablefrom regulatoryagencies.

3. The update search (forunchanged eligibilitycriteria) will normally belimited to materialadded or indexed afterthe date of the previoussearch. The yield of theprevious searches maybe useful to decidewhether the full searchis repeated or whetheronly a subset of sourcesshould be searched forthe update.

4. The original databasesearch strategies mayneed to be modified, for

See Handbook Section IV.3.4

Study flow diagrams inCochrane systematic reviewupdates: an adapted PRISMAflow diagram

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example by addingsearch terms, addingnew database subjectheadings, or byremoving unhelpfulsearch terms thatidentified manyirrelevant studies in theoriginal search.

MECIR update standards U6and UR3

U5 Reconsidering data collectionand analysis methods

Mandatory

Consider whether methods fordata collection and analysis(including a GRADEassessment) need to beamended in the light of recentmethodological developments.

Decide if changes are requiredto make better use of existingdata or to incorporate new databy referring to the currentversion of the Handbook.Recent developments in ’Riskof bias’ assessment, statisticalmethods or narrative synthesisapproaches may lead to moreinclusive or more robustsynthesis of the evidence.

The GRADE assessment willrequire evaluation of risk ofbias, inconsistency,imprecision, indirectness andpublication bias. See MECIRupdate standard U11.

If a ‘Summary of findings’ tableis not included in the currentversion, decide on the mainoutcomes and comparisons tobe included and ensure that therelevant data have been (or willbe) collected. See MECIRupdate standard UR5

MECIR update standardsU9-U10

Planning GRADE and SoFtables.

Conduct standards specific to updates (U6-U11)

Conduct standards specific to updates

Standard Rationale and elaboration ResourcesU6 Searching Mandatory Undertake a new search An updated review must

include an update search fornew (or additional) studies. Forissues to consider in planningthe search, see MECIR updatestandard U4.

See Handbook Section IV.4and Section 4.4.10

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The most recent search mustbe no more than 12 months(preferably six months) from theintended publication date, andthe results screened forpotentially eligible studies.

See MECIR conduct standardC37: Rerun or update searchesfor all relevant databases within12 months before publication ofthe review or review update,and screen the results forpotentially eligible studies.

U7 Including new studies Mandatory Implement conduct standards

for study selection and datacollection for any newlyidentified studies (with updatedcriteria or methods asdetermined above).

MECIR conduct standardsC39 - C51

See Handbook Section 4.4.6, Section 5.3.6, Section 4.6.3, Section 4.6.4, Section 4.6.2, Section 5.2, Section 5.2.1, Section 5.2.3, Section 5.3.1, Section 5.3.6, Section 5.4.1 andSection 5.5.2

U8 Reconsider previouslyidentified studies

Mandatory

Consider studies previouslyidentified as included, awaitingclassification, ongoing andexcluded, and collect additionalinformation from them ifnecessary.

Ensure appropriatemethodology is followed toselect included studies andcollect information from them.

It will be necessary to establishwhether any studies previouslyidentified as ongoing have nowbeen completed.

Ensure that reasons forexcluding studies areconsistent with current eligibilitycriteria and methodologicalstandards.

A redesign of the datacollection form may be requiredif review questions or objectiveshave been modified.

U9 Assessing risk of bias Mandatory Ensure all studies are

consistently assessed for risk ofbias.

The updated review mustinclude a ‘Risk of bias’assessment of all new andpreviously included studies. Ifthe previous version used theoriginal risk of bias tool toassess randomised trials,consider whether or not toswitch to the Risk of Bias 2 tool(see Handbook (version 6)Chapter 8), including how manyrandomised trials wereassessed in the previousversion, how many new studiesare expected for inclusion in the

See Handbook Section 7.1.2, Section 7.3.2, Section 7.5, Section 7.6.1, Section 7.8.6 andChapter 8.

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update, how well it wasimplemented in the previousversion and whether it isfeasible to switch.

MECIR conduct standardsC52 - C60

U10 Synthesizing results Mandatory Implement review synthesis

methods (possibly revised forthe update) according toconduct standards forsynthesis, across all includedstudies.

MECIR conduct standards C61 - C73

See Handbook Section 6.2.1, Section 6.2.9, Section 10.5.3, Section 10.10.2, Section10.10.3, Section 10.11.3.1, Section 10.11.5.2, Section10.12.1, Section 10.14,Chapter 11, Section 13.4, Section 15.3.1

U11 Assessing the certainty ofevidence

Mandatory

Assess certainty of evidenceusing GRADE considerations ofrisk of bias, inconsistency,imprecision, indirectness andpublication bias.

This must be applied to the fullbody of evidence for the keyoutcomes included in theupdated review. The mostconvenient way to presentGRADE assessments is in a‘Summary of findings’ table.

MECIR conduct standardsC74-C75 and MECIR reportingstandard R97


Reporting standards specific to updates (UR1-UR7)

Reporting standards specific to updates

Standard Rationale and elaboration ResourcesUR1 Background Mandatory Review and update background

as necessary to reflect changesover time.

Examples of changes thatshould be addressed includeupdated estimates of diseaseburden, new understanding ofhow people are affected by thedisease or condition, newinsights into mechanisms ofaction, or changes in policy orpractice. Up-to-date referencesshould be supplied to supportthis information.

See Handbook Section IV.5

UR2 Changes to scope Mandatory Explain any changes to

questions, objectives oreligibility criteria.

Motivations to amend reviewquestions and objectives for theupdate (such as addition of newinterventions, or concerns overadverse effects) should beexplained in the Background,and changes to eligibility

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criteria should be explained,dated and justified as‘Differences between theprotocol and the review’.

UR3 Search for studies Mandatory Describe the update search. Describe which sources of

information were searched forthe update, and how. If any ofthe sources originally searchedwere not searched for theupdate, this should beexplained and justified. Thereare at least four possibilities forproviding information aboutsearch methods in an updatedreview:

1. An integrated approachis to describe allsearches together,which may be mostfeasible if the samesearch was repeated.

2. An incrementalapproach is to addinformation at eachupdate to describeexplicitly whichsearches were done forthe update, retaining allinformation aboutprevious searches.

3. A replacementapproach is to describeonly the searches donefor the update, using theprevious review as onesource of studies.

4. A hybrid approach is todescribe only thesearches done for theupdate in the main text,using Appendices toprovide informationabout previoussearches.


UR4 Flow of studies Mandatory Record the flow of studies. Provide information on the flow

of studies into the updatedreview, using a PRISMA typeflow diagram. There are twobroad options for providinginformation about how studieswere identified that are includedin the updated version of thereview:

1. The results of previoussearches can beretained in the review


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and supplemented withinformation aboutstudies identified in theupdate.

2. Alternatively, onlyinformation aboutsearches in the currentupdate can bepresented, with theprevious version of thereview serving as oneparticular source ofstudies.

Either approach is acceptable.If taking the latter approach, theflow diagram should show onebox for the number of studiesincluded in the original reviewor previous update and anadditional box for the newstudies retrieved for the currentupdate. If multiple searcheshave been conducted for thecurrent update, the results of allthe searches should be addedtogether.

UR5 "Summary of findings" tables Highly desirable Present a ‘Summary of findings’

table according torecommendations described inthe Handbook (version 5 orlater). Specifically, includeresults for one clearly definedpopulation group (with fewexceptions).

Efforts should be made toincorporate informationpresented in ‘Summary offindings’ tables (such asabsolute effects, GRADEcertainty ratings anddowngrading decisions) in otherparts of the review including theAbstract, Plain languagesummary, Effects ofinterventions, Discussion andAuthors’ conclusions.


Common issues in Summary ofFindings tables

UR6 Integrating findings Mandatory Present findings integrated

across new and previouslyincluded studies and not just forthe new studies (in the maintext, Abstract, ‘Summary offindings’ tables and Plainlanguage summary).

The main findings should bepresented for the totality ofevidence: it is not helpful to anew reader to be told aboutincremental updates to theevidence base. However, theimpact of new evidence onreview findings may be usefulto draw on when interpretingthe results.

UR7 What's new? Mandatory Explain what’s new. It is important that changes are

explained to inform returningreaders about what’s new. Thisshould be achieved in severalways.

A comment should be insertedto explain that the review is an


Common issues in Summary ofFindings tables

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update of a previouslypublished review. This might beplaced at the beginning or endof the Background or the startof the section ‘Search methodsfor identification of studies’. Itcan be helpful to explain alsowhether the article describesthe first, second, third and soon update of the review.

Changes in review questions,eligibility criteria and methodsshould be reported in thesection ‘Differences betweenprotocol and review’, making itclear that they are changessince the previous version.

Changes in findings must bereported and dated in the‘What’s new’ section. Thisshould include the numbers ofnew studies and participants inthose studies; and the nature ofany changes in assessments ofthe certainty of the evidence(e.g. using GRADE) and in theclinical implications of thefindings. For particularlynotable changes it is useful tocomment on these within thetext of the review.

Citation

Citation for the Standards for the planning, conduct and reporting of updates of CochraneIntervention Reviews

Please cite this section as: Chandler J, Lasserson T, Higgins JPT, Tovey D, Thomas J, Flemyng E, Churchill R. Standards for theplanning, conduct and reporting of updates of Cochrane Intervention Reviews. In: Higgins JPT, Lasserson T, Chandler J, Tovey D,Thomas J, Flemyng E, Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, February2021.

Translations of the MECIR Standards Key points and introductionKey points:

Cochrane encourages translations of the MECIR Manual in order to support the engagement of people withdifferent native languages in Cochrane Review production.Full details on the conditions and process for translating the MECIR Manual can be found in the CochraneMECIR translations guidance

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If you are interested in translating the MECIR Manual, contact [email protected].

The Cochrane Editorial and Methods Department, Knowledge Translation Department and authors of the MECIR Standardsencourage translations of the MECIR Standards in order to support the engagement of people with different native languages inCochrane Review production.

The MECIR Standards are the ‘how-to’ guides for conducting, reporting and updating Cochrane Intervention Reviews, Protocolsand Updates. The MECIR Standards for the conduct of new Cochrane Intervention Reviews are embedded throughout the Cochrane Handbook for Systematic Reviews of Interventions.

Translation proposals will be assessed and approved by the Cochrane Methods team and the Translations Coordinator. Please seethe Cochrane MECIR translations guidance for full details on the conditions that must be met for MECIR translations, how to initiatea MECIR translation and keeping it up-to-date.

If you are interested in translating the MECIR Manual, or have any questions about the process or other general queries, pleasecontact [email protected].

Japanese translationMECIR is available in Japanese.

You can open the Japanese translation as a PDF here (February 2021).

Previous versions are available below:

March 2020 Japanese translation PDF here

Russian translation MECIR is available in Russian.

You can open the Russian translation as a PDF here (February 2021).

Spanish translationMECIR is available in Spanish.

You can open the Spanish translation as a PDF here (February 2021).

Previous versions are available below:

March 2020 Spanish translation here.

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